TBD Meeting (3042-21)

Gastroenterologists should be skilled in recognition of patients with inherited risk of colorectal neoplasia. During the session on colonic diseases, the case presentations provided tools to help clinicians identify and evaluate high-risk individuals. Fay Kastrinos, MD, presented a 49-year-old female who had more than 10 cumulative adenomas and a cecal adenocarcinoma on two colonoscopies, the first of which was performed for evaluation of rectal bleeding. Carol Burke, MD, reviewed the differential diagnosis of adenomatous polyposis (defined as >10 cumulative adenomas).

Germline syndromes include familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and a number of rare germline syndromes. Lynch syndrome should be considered especially for carriers of pathogenic variants in MSH6 who can present with a polyposis phenotype, as well as in children with constitutional mismatch repair deficiency syndrome. Finally, polyposis can be due to smoking, familial clustering, or previous abdominal radiation called therapy-associated polyposis. Polyposis without a known cause is referred to as colonic polyposis of unknown etiology (CPUE).

Dr. Kastrinos reviewed the patient’s three-generation family history of a brother and mother with “polyps” and second-degree relatives with endometrial and colon cancer. Niloy Jewel Samadder, MD, presented on the role of taking a comprehensive family history, tumor tests for Lynch syndrome, selection of genetic test type, and risks, benefits, and alternatives of genetic testing. Dr. Samadder reviewed indications for germline genetic testing for colorectal neoplasia of which the patient met two criteria, namely colorectal cancer under age 50 and 10 or more cumulative adenomas.

The final section was presented by this author on multigene panel testing, in which multiple genes are sequenced simultaneously. This patient’s panel showed two pathogenic variants in the MUTYH gene consistent with MAP, a recessive polyposis syndrome typically with 10s-100 cumulative adenomas. The test also showed a variant of uncertain significance (VUS) which is not clinically actionable. Providers counseling patients on multigene panel testing should discuss the possibility of VUS results (especially in individuals of non-European descent), moderate penetrant genes for which management recommendations are uncertain, or unexpected findings in genes not associated with colonic neoplasia. Studies have shown that the prevalence of finding an inherited syndrome is increased at younger ages of disease onset.

Dr. Kastrinos summarized key points from the session, including hereditary colorectal cancer syndromes are not rare, red flags for inherited syndromes, include early onset colorectal neoplasia and/or numerous relatives with colorectal and other extra-colonic cancer, extended family history assessment is recommended, and genetic risk assessment and genetic testing with multigene panels is a process and should be personalized. The question and answer session was lively with discussion of cost as well as direct-to-consumer genetic testing.

Sonia Kupfer, MD, AGAF, is an associate professor in the section of gastroenterology, hepatology, and nutrition at the University of Chicago. She has no financial conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.

Gastroenterologists should be skilled in recognition of patients with inherited risk of colorectal neoplasia. During the session on colonic diseases, the case presentations provided tools to help clinicians identify and evaluate high-risk individuals. Fay Kastrinos, MD, presented a 49-year-old female who had more than 10 cumulative adenomas and a cecal adenocarcinoma on two colonoscopies, the first of which was performed for evaluation of rectal bleeding. Carol Burke, MD, reviewed the differential diagnosis of adenomatous polyposis (defined as >10 cumulative adenomas).

Germline syndromes include familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and a number of rare germline syndromes. Lynch syndrome should be considered especially for carriers of pathogenic variants in MSH6 who can present with a polyposis phenotype, as well as in children with constitutional mismatch repair deficiency syndrome. Finally, polyposis can be due to smoking, familial clustering, or previous abdominal radiation called therapy-associated polyposis. Polyposis without a known cause is referred to as colonic polyposis of unknown etiology (CPUE).

Dr. Kastrinos reviewed the patient’s three-generation family history of a brother and mother with “polyps” and second-degree relatives with endometrial and colon cancer. Niloy Jewel Samadder, MD, presented on the role of taking a comprehensive family history, tumor tests for Lynch syndrome, selection of genetic test type, and risks, benefits, and alternatives of genetic testing. Dr. Samadder reviewed indications for germline genetic testing for colorectal neoplasia of which the patient met two criteria, namely colorectal cancer under age 50 and 10 or more cumulative adenomas.

The final section was presented by this author on multigene panel testing, in which multiple genes are sequenced simultaneously. This patient’s panel showed two pathogenic variants in the MUTYH gene consistent with MAP, a recessive polyposis syndrome typically with 10s-100 cumulative adenomas. The test also showed a variant of uncertain significance (VUS) which is not clinically actionable. Providers counseling patients on multigene panel testing should discuss the possibility of VUS results (especially in individuals of non-European descent), moderate penetrant genes for which management recommendations are uncertain, or unexpected findings in genes not associated with colonic neoplasia. Studies have shown that the prevalence of finding an inherited syndrome is increased at younger ages of disease onset.

Dr. Kastrinos summarized key points from the session, including hereditary colorectal cancer syndromes are not rare, red flags for inherited syndromes, include early onset colorectal neoplasia and/or numerous relatives with colorectal and other extra-colonic cancer, extended family history assessment is recommended, and genetic risk assessment and genetic testing with multigene panels is a process and should be personalized. The question and answer session was lively with discussion of cost as well as direct-to-consumer genetic testing.

Sonia Kupfer, MD, AGAF, is an associate professor in the section of gastroenterology, hepatology, and nutrition at the University of Chicago. She has no financial conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.

Gastroenterologists should be skilled in recognition of patients with inherited risk of colorectal neoplasia. During the session on colonic diseases, the case presentations provided tools to help clinicians identify and evaluate high-risk individuals. Fay Kastrinos, MD, presented a 49-year-old female who had more than 10 cumulative adenomas and a cecal adenocarcinoma on two colonoscopies, the first of which was performed for evaluation of rectal bleeding. Carol Burke, MD, reviewed the differential diagnosis of adenomatous polyposis (defined as >10 cumulative adenomas).

Germline syndromes include familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and a number of rare germline syndromes. Lynch syndrome should be considered especially for carriers of pathogenic variants in MSH6 who can present with a polyposis phenotype, as well as in children with constitutional mismatch repair deficiency syndrome. Finally, polyposis can be due to smoking, familial clustering, or previous abdominal radiation called therapy-associated polyposis. Polyposis without a known cause is referred to as colonic polyposis of unknown etiology (CPUE).

Dr. Kastrinos reviewed the patient’s three-generation family history of a brother and mother with “polyps” and second-degree relatives with endometrial and colon cancer. Niloy Jewel Samadder, MD, presented on the role of taking a comprehensive family history, tumor tests for Lynch syndrome, selection of genetic test type, and risks, benefits, and alternatives of genetic testing. Dr. Samadder reviewed indications for germline genetic testing for colorectal neoplasia of which the patient met two criteria, namely colorectal cancer under age 50 and 10 or more cumulative adenomas.

The final section was presented by this author on multigene panel testing, in which multiple genes are sequenced simultaneously. This patient’s panel showed two pathogenic variants in the MUTYH gene consistent with MAP, a recessive polyposis syndrome typically with 10s-100 cumulative adenomas. The test also showed a variant of uncertain significance (VUS) which is not clinically actionable. Providers counseling patients on multigene panel testing should discuss the possibility of VUS results (especially in individuals of non-European descent), moderate penetrant genes for which management recommendations are uncertain, or unexpected findings in genes not associated with colonic neoplasia. Studies have shown that the prevalence of finding an inherited syndrome is increased at younger ages of disease onset.

Dr. Kastrinos summarized key points from the session, including hereditary colorectal cancer syndromes are not rare, red flags for inherited syndromes, include early onset colorectal neoplasia and/or numerous relatives with colorectal and other extra-colonic cancer, extended family history assessment is recommended, and genetic risk assessment and genetic testing with multigene panels is a process and should be personalized. The question and answer session was lively with discussion of cost as well as direct-to-consumer genetic testing.

Sonia Kupfer, MD, AGAF, is an associate professor in the section of gastroenterology, hepatology, and nutrition at the University of Chicago. She has no financial conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.

As an esophagologist that does not perform fundoplication, LINX, or TIF, I find it difficult to debate the merits of one procedure over another based on my experience. In fact, I have always stated that it is difficult to assess a procedure or test that one has not used. That being said, maybe the fact that I have not performed these procedures makes me more objective and I can only use my experience with patients and the data to make the case that we need options beyond Nissen fundoplication.

The recent VA Randomized trial in refractory GERD published by Spechler and colleagues once again highlighted the fact that there are some patients that require a mechanical solution to reflux disease.¹ In this study, the authors carefully defined a patient population with refractory GERD and showed that Nissen fundoplication was superior to medical management in patients who did not respond to proton pump inhibitors. However, of the 27 patients who underwent fundoplication, one patient had major complications which required a repeat operation and prolonged hospital stay. These findings highlight the main problem with Nissen fundoplication. Dr. Watson elegantly argued in his assertion during our debate that Nissen and fundoplication are not the same. In this position, he was noting the side effects associated with Nissen fundoplication,² and he focused his argument on the comparison between a partial wrap versus LINX and TIF to level the playing field. On that note, I agree with Dr. Watson that a well-done partial fundoplication is a great option for patients with a mechanical problem.

Nonetheless, I think we have the capacity to do better than Nissen fundoplication, and thus, a safer standardized reversible surgical option and a less invasive endoscopic approach have great appeal. Redo operations have an escalating risk of severe debilitating consequences and we should do everything possible to reduce that risk.³ The LINX and the TIF procedure have data to support their effectiveness, and the initial studies suggest a more favorable side effect profile.^4,5 The ability to perform these procedures in patients with hiatal hernia and the fact that these approaches do not exclude the possibility of fundoplication in the future make them an attractive alternative.

In the end, more rigorous comparative studies should be performed to truly determine which approach is better. Although we have good surgical and medical options, we all recognize that they are not perfect and we should not settle on the current state of GERD management.

John E. Pandolfino, MD, MSCI, is the Hans Popper Professor of Medicine and Division Chief, Gastroenterology and Hepatology at Northwestern University, Chicago. He disclosed relationships with Ethicon/Johnson & Johnson, Endogastric Solutions, and Medtronic. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.

References

1. Spechler SJ et al. N Engl J Med. 2019 Oct 17;381[16]:1513-23.

2. Yadlapati R et al. Am J Gastroenterol. 2018 Aug;113[8]:1137-47.

3. Singhal S et al. J Gastrointest Surg. 2018 Feb;22[2]:177-86.

4. Ganz RA et al. Clin Gastroenterol Hepatol. 2016 May;14(5):671-7.

5. Testoni PA et al. Endosc Int Open. 2019 May;7(5):E647-E654.

As an esophagologist that does not perform fundoplication, LINX, or TIF, I find it difficult to debate the merits of one procedure over another based on my experience. In fact, I have always stated that it is difficult to assess a procedure or test that one has not used. That being said, maybe the fact that I have not performed these procedures makes me more objective and I can only use my experience with patients and the data to make the case that we need options beyond Nissen fundoplication.

The recent VA Randomized trial in refractory GERD published by Spechler and colleagues once again highlighted the fact that there are some patients that require a mechanical solution to reflux disease.¹ In this study, the authors carefully defined a patient population with refractory GERD and showed that Nissen fundoplication was superior to medical management in patients who did not respond to proton pump inhibitors. However, of the 27 patients who underwent fundoplication, one patient had major complications which required a repeat operation and prolonged hospital stay. These findings highlight the main problem with Nissen fundoplication. Dr. Watson elegantly argued in his assertion during our debate that Nissen and fundoplication are not the same. In this position, he was noting the side effects associated with Nissen fundoplication,² and he focused his argument on the comparison between a partial wrap versus LINX and TIF to level the playing field. On that note, I agree with Dr. Watson that a well-done partial fundoplication is a great option for patients with a mechanical problem.

Nonetheless, I think we have the capacity to do better than Nissen fundoplication, and thus, a safer standardized reversible surgical option and a less invasive endoscopic approach have great appeal. Redo operations have an escalating risk of severe debilitating consequences and we should do everything possible to reduce that risk.³ The LINX and the TIF procedure have data to support their effectiveness, and the initial studies suggest a more favorable side effect profile.^4,5 The ability to perform these procedures in patients with hiatal hernia and the fact that these approaches do not exclude the possibility of fundoplication in the future make them an attractive alternative.

In the end, more rigorous comparative studies should be performed to truly determine which approach is better. Although we have good surgical and medical options, we all recognize that they are not perfect and we should not settle on the current state of GERD management.

John E. Pandolfino, MD, MSCI, is the Hans Popper Professor of Medicine and Division Chief, Gastroenterology and Hepatology at Northwestern University, Chicago. He disclosed relationships with Ethicon/Johnson & Johnson, Endogastric Solutions, and Medtronic. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.

References

1. Spechler SJ et al. N Engl J Med. 2019 Oct 17;381[16]:1513-23.

2. Yadlapati R et al. Am J Gastroenterol. 2018 Aug;113[8]:1137-47.

3. Singhal S et al. J Gastrointest Surg. 2018 Feb;22[2]:177-86.

4. Ganz RA et al. Clin Gastroenterol Hepatol. 2016 May;14(5):671-7.

5. Testoni PA et al. Endosc Int Open. 2019 May;7(5):E647-E654.

As an esophagologist that does not perform fundoplication, LINX, or TIF, I find it difficult to debate the merits of one procedure over another based on my experience. In fact, I have always stated that it is difficult to assess a procedure or test that one has not used. That being said, maybe the fact that I have not performed these procedures makes me more objective and I can only use my experience with patients and the data to make the case that we need options beyond Nissen fundoplication.

The recent VA Randomized trial in refractory GERD published by Spechler and colleagues once again highlighted the fact that there are some patients that require a mechanical solution to reflux disease.¹ In this study, the authors carefully defined a patient population with refractory GERD and showed that Nissen fundoplication was superior to medical management in patients who did not respond to proton pump inhibitors. However, of the 27 patients who underwent fundoplication, one patient had major complications which required a repeat operation and prolonged hospital stay. These findings highlight the main problem with Nissen fundoplication. Dr. Watson elegantly argued in his assertion during our debate that Nissen and fundoplication are not the same. In this position, he was noting the side effects associated with Nissen fundoplication,² and he focused his argument on the comparison between a partial wrap versus LINX and TIF to level the playing field. On that note, I agree with Dr. Watson that a well-done partial fundoplication is a great option for patients with a mechanical problem.

Nonetheless, I think we have the capacity to do better than Nissen fundoplication, and thus, a safer standardized reversible surgical option and a less invasive endoscopic approach have great appeal. Redo operations have an escalating risk of severe debilitating consequences and we should do everything possible to reduce that risk.³ The LINX and the TIF procedure have data to support their effectiveness, and the initial studies suggest a more favorable side effect profile.^4,5 The ability to perform these procedures in patients with hiatal hernia and the fact that these approaches do not exclude the possibility of fundoplication in the future make them an attractive alternative.

In the end, more rigorous comparative studies should be performed to truly determine which approach is better. Although we have good surgical and medical options, we all recognize that they are not perfect and we should not settle on the current state of GERD management.

John E. Pandolfino, MD, MSCI, is the Hans Popper Professor of Medicine and Division Chief, Gastroenterology and Hepatology at Northwestern University, Chicago. He disclosed relationships with Ethicon/Johnson & Johnson, Endogastric Solutions, and Medtronic. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.

References

1. Spechler SJ et al. N Engl J Med. 2019 Oct 17;381[16]:1513-23.

2. Yadlapati R et al. Am J Gastroenterol. 2018 Aug;113[8]:1137-47.

3. Singhal S et al. J Gastrointest Surg. 2018 Feb;22[2]:177-86.

4. Ganz RA et al. Clin Gastroenterol Hepatol. 2016 May;14(5):671-7.

5. Testoni PA et al. Endosc Int Open. 2019 May;7(5):E647-E654.

Days after the World Health Organization declared the COVID-19 outbreak a global pandemic, Pfizer and BioNTech announced plans to codevelop a potential mRNA-based vaccine to help prevent COVID-19. The mRNA platform was selected given its potential for high potency and capacity for rapid development. A bold decision was made to invest in R&D and manufacturing at risk.

Two candidates, BNT162b1 and BNT162b2, quickly emerged as most promising. After extensive review of preclinical and early clinical data and in consultation with regulators, we advanced BNT162b2 into a global, Phase 2/3 efficacy trial in July 2020.

The study prioritized participant diversity from the beginning, including selecting trial sites in communities disproportionally affected by COVID-19. Enrollment was later expanded to increase diversity, and also to include adolescents 12 and older and people with chronic, stable HIV, Hepatitis C, or Hepatitis B.

In November 2020, we announced the results of our ongoing Phase 3 study with BNT162b2 demonstrating a vaccine efficacy rate of 95% against COVID-19 beginning 28 days after dose one. This result showed our ability to leverage decades of scientific expertise to execute a rigorous Phase 3 clinical program to make a potential vaccine available as quickly and safely as possible. The emergency use authorization that followed was a big step, but our research did not stop there.

Pfizer and BioNTech continue to evaluate data from the landmark trial, which ultimately enrolled 46,331 participants. We are also conducting trials in special populations, such as pregnant women and children under 12. To date, real-world evidence has demonstrated lower COVID-19 incidence in vaccinated individuals and has not shown escape of variant viruses from BNT162b2-mediated protection. Studies are ongoing to explore the effect of a third dose on immunity and to prepare in case a variant emerges that escapes protection.

We continue to identify improvements to increase production and are on track to deliver approximately 2.5 billion doses in 2021. Next generation ready-to-use and freeze-dried formulations are in development.

This pandemic sparked an unparalleled period of innovation, investment, and partnership with lessons learned that will help us prepare for future pandemics and accelerate R&D of therapeutic candidates for other debilitating and life-threatening conditions.

The Pfizer-BioNTech COVID-19 vaccine has not been approved or licensed by the U.S. Food and Drug Administration but has been authorized for emergency use to prevent COVID-19 in individuals 12+. See conditions of use: http://cvdvaccine.com

Dr. Dolsten is the Chief Scientific Officer and President of Worldwide Research, Development and Medical at Pfizer. He has no other conflicts. Dr. Dolsten made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

Days after the World Health Organization declared the COVID-19 outbreak a global pandemic, Pfizer and BioNTech announced plans to codevelop a potential mRNA-based vaccine to help prevent COVID-19. The mRNA platform was selected given its potential for high potency and capacity for rapid development. A bold decision was made to invest in R&D and manufacturing at risk.

Two candidates, BNT162b1 and BNT162b2, quickly emerged as most promising. After extensive review of preclinical and early clinical data and in consultation with regulators, we advanced BNT162b2 into a global, Phase 2/3 efficacy trial in July 2020.

The study prioritized participant diversity from the beginning, including selecting trial sites in communities disproportionally affected by COVID-19. Enrollment was later expanded to increase diversity, and also to include adolescents 12 and older and people with chronic, stable HIV, Hepatitis C, or Hepatitis B.

In November 2020, we announced the results of our ongoing Phase 3 study with BNT162b2 demonstrating a vaccine efficacy rate of 95% against COVID-19 beginning 28 days after dose one. This result showed our ability to leverage decades of scientific expertise to execute a rigorous Phase 3 clinical program to make a potential vaccine available as quickly and safely as possible. The emergency use authorization that followed was a big step, but our research did not stop there.

Pfizer and BioNTech continue to evaluate data from the landmark trial, which ultimately enrolled 46,331 participants. We are also conducting trials in special populations, such as pregnant women and children under 12. To date, real-world evidence has demonstrated lower COVID-19 incidence in vaccinated individuals and has not shown escape of variant viruses from BNT162b2-mediated protection. Studies are ongoing to explore the effect of a third dose on immunity and to prepare in case a variant emerges that escapes protection.

We continue to identify improvements to increase production and are on track to deliver approximately 2.5 billion doses in 2021. Next generation ready-to-use and freeze-dried formulations are in development.

This pandemic sparked an unparalleled period of innovation, investment, and partnership with lessons learned that will help us prepare for future pandemics and accelerate R&D of therapeutic candidates for other debilitating and life-threatening conditions.

The Pfizer-BioNTech COVID-19 vaccine has not been approved or licensed by the U.S. Food and Drug Administration but has been authorized for emergency use to prevent COVID-19 in individuals 12+. See conditions of use: http://cvdvaccine.com

Dr. Dolsten is the Chief Scientific Officer and President of Worldwide Research, Development and Medical at Pfizer. He has no other conflicts. Dr. Dolsten made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

Days after the World Health Organization declared the COVID-19 outbreak a global pandemic, Pfizer and BioNTech announced plans to codevelop a potential mRNA-based vaccine to help prevent COVID-19. The mRNA platform was selected given its potential for high potency and capacity for rapid development. A bold decision was made to invest in R&D and manufacturing at risk.

Two candidates, BNT162b1 and BNT162b2, quickly emerged as most promising. After extensive review of preclinical and early clinical data and in consultation with regulators, we advanced BNT162b2 into a global, Phase 2/3 efficacy trial in July 2020.

The study prioritized participant diversity from the beginning, including selecting trial sites in communities disproportionally affected by COVID-19. Enrollment was later expanded to increase diversity, and also to include adolescents 12 and older and people with chronic, stable HIV, Hepatitis C, or Hepatitis B.

In November 2020, we announced the results of our ongoing Phase 3 study with BNT162b2 demonstrating a vaccine efficacy rate of 95% against COVID-19 beginning 28 days after dose one. This result showed our ability to leverage decades of scientific expertise to execute a rigorous Phase 3 clinical program to make a potential vaccine available as quickly and safely as possible. The emergency use authorization that followed was a big step, but our research did not stop there.

Pfizer and BioNTech continue to evaluate data from the landmark trial, which ultimately enrolled 46,331 participants. We are also conducting trials in special populations, such as pregnant women and children under 12. To date, real-world evidence has demonstrated lower COVID-19 incidence in vaccinated individuals and has not shown escape of variant viruses from BNT162b2-mediated protection. Studies are ongoing to explore the effect of a third dose on immunity and to prepare in case a variant emerges that escapes protection.

We continue to identify improvements to increase production and are on track to deliver approximately 2.5 billion doses in 2021. Next generation ready-to-use and freeze-dried formulations are in development.

This pandemic sparked an unparalleled period of innovation, investment, and partnership with lessons learned that will help us prepare for future pandemics and accelerate R&D of therapeutic candidates for other debilitating and life-threatening conditions.

The Pfizer-BioNTech COVID-19 vaccine has not been approved or licensed by the U.S. Food and Drug Administration but has been authorized for emergency use to prevent COVID-19 in individuals 12+. See conditions of use: http://cvdvaccine.com

Dr. Dolsten is the Chief Scientific Officer and President of Worldwide Research, Development and Medical at Pfizer. He has no other conflicts. Dr. Dolsten made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

Ustekinumab (Stelara, Janssen) appears superior to vedolizumab (Entyvio, Takeda) on multiple measures of response and remission among patients with Crohn’s disease who failed at least one anti–tumor necrosis factor (TNF) therapy, in a retrospective analysis.

Of patients taking ustekinumab, a higher proportion (51%) met the primary endpoint of corticosteroid-free clinical remission at week 54. In the vedolizumab group, only 41% achieved the same outcome.

“Failure to anti-TNF therapy is a major concern in Crohn’s disease,” Anthony Buisson, MD, PhD, head of the Inflammatory Bowel Disease Unit, University Hospital Estaing, Clermont-Ferrand, France, said during the Digestive Disease Week 2021 virtual meeting.

Dr. Buisson estimated that 15% of patients with Crohn’s disease experience primary failure from an anti-TNF agent. Also, only slightly more than one-third (37%) remain in clinical remission at 1 year.

With that in mind, Dr. Buisson and his colleagues conducted the VENUS study to evaluate outcomes between ustekinumab and vedolizumab. These two biologic agents are indicated for Crohn’s disease and feature different mechanisms of action, compared with anti-TNF agents.

They assessed 312 adults with Crohn’s disease from two patient cohorts in France. All participants failed prior treatment with at least one anti-TNF agent, including approximately 20% who experienced a primary nonresponse.

The retrospective analysis included 224 patients treated with ustekinumab and another 88 with vedolizumab between July 2014 and May 2020. The two groups were comparable based on a propensity analysis. Other medications were allowed at the physician’s discretion.
 

Nonresponders and other outcomes

“Vedolizumab patients were more likely to be primary nonresponders than ustekinumab patients,” Dr. Buisson said. This group included 6% of patients taking ustekinumab versus 14% of those taking vedolizumab.

In contrast, regarding secondary loss of response, “we did not observe any [significant] difference between two groups,” he added.

The investigators defined corticosteroid-free remission as a Crohn’s Disease Activity Index less than 150 at week 54. They also assessed “deep remission” at 14 weeks, which was defined as meeting corticosteroid-free remission and a fecal calprotectin of less than 100 mcg/g.

They found that 26% of patients who received ustekinumab met the deep remission criteria versus 4% of those who received vedolizumab.

Dr. Buisson and colleagues also looked at time to drug escalation. A Kaplan Meier curve revealed that patients taking vedolizumab were more likely to be escalated, compared with those taking ustekinumab (hazard ratio, 1.35).

Furthermore, those treated with vedolizumab also featured a higher risk for drug discontinuation because of therapeutic failure (HR, 1.53).

“This is an interesting study comparing ustekinumab with vedolizumab in Crohn’s disease patients who have failed prior anti-TNF therapy,” Farah Monzur, MD, who was not affiliated with the study, told this news organization. “Although the researchers assessed corticosteroid-free remission and ‘deep remission,’ ” she said, endoscopic and histologic remission were not studied, “which have become the new targets to achieve.”

“Even so, this study adds to the literature, aiming to position these newer biologics in the treatment algorithm,” added Dr. Monzur, assistant professor of medicine and medical director of ambulatory GI at Stony Brook (N.Y.) Medicine.
 

Superior in subgroup analyses as well

“No subgroups were identified where vedolizumab was more effective than ustekinumab,” Dr. Buisson said. “In contrast, ustekinumab was more effective in five subgroups.”

The subgroups favoring ustekinumab included those patients not taking steroids at baseline, with no prior bowel resection, with a noncomplicated phenotype, with upper gastrointestinal involvement, and older than 35 years of age.

The retrospective analysis design was a limitation. The long follow-up and large sample size were strengths.

The authors concluded that ustekinumab was more effective to achieve early and long-term efficacy than vedolizumab in patients with Crohn’s disease who previously failed to anti-TNF agents.

“However, these data should be confirmed in a head-to-head randomized controlled trial,” Dr. Buisson said.

Dr. Buisson disclosed that he is a consultant for Janssen and Takeda. Dr. Monzur has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com..

Ustekinumab (Stelara, Janssen) appears superior to vedolizumab (Entyvio, Takeda) on multiple measures of response and remission among patients with Crohn’s disease who failed at least one anti–tumor necrosis factor (TNF) therapy, in a retrospective analysis.

Of patients taking ustekinumab, a higher proportion (51%) met the primary endpoint of corticosteroid-free clinical remission at week 54. In the vedolizumab group, only 41% achieved the same outcome.

“Failure to anti-TNF therapy is a major concern in Crohn’s disease,” Anthony Buisson, MD, PhD, head of the Inflammatory Bowel Disease Unit, University Hospital Estaing, Clermont-Ferrand, France, said during the Digestive Disease Week 2021 virtual meeting.

Dr. Buisson estimated that 15% of patients with Crohn’s disease experience primary failure from an anti-TNF agent. Also, only slightly more than one-third (37%) remain in clinical remission at 1 year.

With that in mind, Dr. Buisson and his colleagues conducted the VENUS study to evaluate outcomes between ustekinumab and vedolizumab. These two biologic agents are indicated for Crohn’s disease and feature different mechanisms of action, compared with anti-TNF agents.

They assessed 312 adults with Crohn’s disease from two patient cohorts in France. All participants failed prior treatment with at least one anti-TNF agent, including approximately 20% who experienced a primary nonresponse.

The retrospective analysis included 224 patients treated with ustekinumab and another 88 with vedolizumab between July 2014 and May 2020. The two groups were comparable based on a propensity analysis. Other medications were allowed at the physician’s discretion.
 

Nonresponders and other outcomes

“Vedolizumab patients were more likely to be primary nonresponders than ustekinumab patients,” Dr. Buisson said. This group included 6% of patients taking ustekinumab versus 14% of those taking vedolizumab.

In contrast, regarding secondary loss of response, “we did not observe any [significant] difference between two groups,” he added.

The investigators defined corticosteroid-free remission as a Crohn’s Disease Activity Index less than 150 at week 54. They also assessed “deep remission” at 14 weeks, which was defined as meeting corticosteroid-free remission and a fecal calprotectin of less than 100 mcg/g.

They found that 26% of patients who received ustekinumab met the deep remission criteria versus 4% of those who received vedolizumab.

Dr. Buisson and colleagues also looked at time to drug escalation. A Kaplan Meier curve revealed that patients taking vedolizumab were more likely to be escalated, compared with those taking ustekinumab (hazard ratio, 1.35).

Furthermore, those treated with vedolizumab also featured a higher risk for drug discontinuation because of therapeutic failure (HR, 1.53).

“This is an interesting study comparing ustekinumab with vedolizumab in Crohn’s disease patients who have failed prior anti-TNF therapy,” Farah Monzur, MD, who was not affiliated with the study, told this news organization. “Although the researchers assessed corticosteroid-free remission and ‘deep remission,’ ” she said, endoscopic and histologic remission were not studied, “which have become the new targets to achieve.”

“Even so, this study adds to the literature, aiming to position these newer biologics in the treatment algorithm,” added Dr. Monzur, assistant professor of medicine and medical director of ambulatory GI at Stony Brook (N.Y.) Medicine.
 

Superior in subgroup analyses as well

“No subgroups were identified where vedolizumab was more effective than ustekinumab,” Dr. Buisson said. “In contrast, ustekinumab was more effective in five subgroups.”

The subgroups favoring ustekinumab included those patients not taking steroids at baseline, with no prior bowel resection, with a noncomplicated phenotype, with upper gastrointestinal involvement, and older than 35 years of age.

The retrospective analysis design was a limitation. The long follow-up and large sample size were strengths.

The authors concluded that ustekinumab was more effective to achieve early and long-term efficacy than vedolizumab in patients with Crohn’s disease who previously failed to anti-TNF agents.

“However, these data should be confirmed in a head-to-head randomized controlled trial,” Dr. Buisson said.

Dr. Buisson disclosed that he is a consultant for Janssen and Takeda. Dr. Monzur has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com..

Ustekinumab (Stelara, Janssen) appears superior to vedolizumab (Entyvio, Takeda) on multiple measures of response and remission among patients with Crohn’s disease who failed at least one anti–tumor necrosis factor (TNF) therapy, in a retrospective analysis.

Of patients taking ustekinumab, a higher proportion (51%) met the primary endpoint of corticosteroid-free clinical remission at week 54. In the vedolizumab group, only 41% achieved the same outcome.

“Failure to anti-TNF therapy is a major concern in Crohn’s disease,” Anthony Buisson, MD, PhD, head of the Inflammatory Bowel Disease Unit, University Hospital Estaing, Clermont-Ferrand, France, said during the Digestive Disease Week 2021 virtual meeting.

Dr. Buisson estimated that 15% of patients with Crohn’s disease experience primary failure from an anti-TNF agent. Also, only slightly more than one-third (37%) remain in clinical remission at 1 year.

With that in mind, Dr. Buisson and his colleagues conducted the VENUS study to evaluate outcomes between ustekinumab and vedolizumab. These two biologic agents are indicated for Crohn’s disease and feature different mechanisms of action, compared with anti-TNF agents.

They assessed 312 adults with Crohn’s disease from two patient cohorts in France. All participants failed prior treatment with at least one anti-TNF agent, including approximately 20% who experienced a primary nonresponse.

The retrospective analysis included 224 patients treated with ustekinumab and another 88 with vedolizumab between July 2014 and May 2020. The two groups were comparable based on a propensity analysis. Other medications were allowed at the physician’s discretion.
 

Nonresponders and other outcomes

“Vedolizumab patients were more likely to be primary nonresponders than ustekinumab patients,” Dr. Buisson said. This group included 6% of patients taking ustekinumab versus 14% of those taking vedolizumab.

In contrast, regarding secondary loss of response, “we did not observe any [significant] difference between two groups,” he added.

The investigators defined corticosteroid-free remission as a Crohn’s Disease Activity Index less than 150 at week 54. They also assessed “deep remission” at 14 weeks, which was defined as meeting corticosteroid-free remission and a fecal calprotectin of less than 100 mcg/g.

They found that 26% of patients who received ustekinumab met the deep remission criteria versus 4% of those who received vedolizumab.

Dr. Buisson and colleagues also looked at time to drug escalation. A Kaplan Meier curve revealed that patients taking vedolizumab were more likely to be escalated, compared with those taking ustekinumab (hazard ratio, 1.35).

Furthermore, those treated with vedolizumab also featured a higher risk for drug discontinuation because of therapeutic failure (HR, 1.53).

“This is an interesting study comparing ustekinumab with vedolizumab in Crohn’s disease patients who have failed prior anti-TNF therapy,” Farah Monzur, MD, who was not affiliated with the study, told this news organization. “Although the researchers assessed corticosteroid-free remission and ‘deep remission,’ ” she said, endoscopic and histologic remission were not studied, “which have become the new targets to achieve.”

“Even so, this study adds to the literature, aiming to position these newer biologics in the treatment algorithm,” added Dr. Monzur, assistant professor of medicine and medical director of ambulatory GI at Stony Brook (N.Y.) Medicine.
 

Superior in subgroup analyses as well

“No subgroups were identified where vedolizumab was more effective than ustekinumab,” Dr. Buisson said. “In contrast, ustekinumab was more effective in five subgroups.”

The subgroups favoring ustekinumab included those patients not taking steroids at baseline, with no prior bowel resection, with a noncomplicated phenotype, with upper gastrointestinal involvement, and older than 35 years of age.

The retrospective analysis design was a limitation. The long follow-up and large sample size were strengths.

The authors concluded that ustekinumab was more effective to achieve early and long-term efficacy than vedolizumab in patients with Crohn’s disease who previously failed to anti-TNF agents.

“However, these data should be confirmed in a head-to-head randomized controlled trial,” Dr. Buisson said.

Dr. Buisson disclosed that he is a consultant for Janssen and Takeda. Dr. Monzur has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com..

A prebiotic therapy in development significantly reduced the number of days per month that people with gastroesophageal reflux disease (GERD) experienced heartburn.

The prebiotic treatment, maltosyl-isomalto-oligosaccharides (MIMO, ISOT-101), under development by ISOThrive, was also associated with reduced symptom severity and improved quality of life, John Selling, MD, chief medical officer at ISOThrive, said during the presentation of his study at the virtual Digestive Disease Week (DDW) 2021.

ISOT-101 is a nondigestible, nonabsorbable prebiotic carbohydrate produced by bacterial fermentation of sucrose and maltose. It was “possibly a staple of the bacterial diet that was present in the human diet during the past 10,000 years,” Dr. Selling said. He is a clinical associate professor of medicine and gastroenterology at Stanford (Calif.) University.

The prebiotic, however, “has been absent in our diet for about 50 to 100 years, driven by changes in agriculture, food production, food preservation, and dietary preferences,” he added.

Acid suppression treatments, such as proton pump inhibitors (PPIs), have long been a staple of treating GERD. However, about 40% of people taking PPIs still have symptoms, Dr. Selling said. He noted that there are concerns about the health risks associated with long-term PPI use.

A prebiotic could work because the distal esophageal microbiome in people with GERD “differs greatly” from that of healthy persons, Dr. Selling said. The prebiotic could help reduce an abnormal increase in gram-negative bacteria in these patients, for example. These bacterial strains express lipopolysaccharides on their outer cell membranes, which, in turn, alter cytokine signaling. This mechanism could lead to the hyperinflammatory state associated with GERD.

Dr. Selling and colleagues hypothesized that this treatment could help resolve GERD symptoms in two ways. The prebiotic could selectively feed the beneficial gram-positive bacteria in the distal esophagus, thereby helping to restore a healthy balance of bacteria. ISOT-101 could also produce bacteriocins that help kill the harmful gram-negative bacteria and control inflammation.

To assess the efficacy and tolerability of ISOT-101, Dr. Selling and colleagues plan to evaluate use of the agent in 110 people with GERD. The data presented at this year’s DDW are based on the first 44 participants to complete the study protocol.

Participants had to have active symptoms four or more days a week. They verbally reported symptoms to investigators and completed a daily ReQuest validated GERD symptom questionnaire.

After a week of baseline screening, participants consumed about a quarter teaspoon of ISOT-101 as the last substance swallowed before bed every night. The investigators asked participants to rate their GI symptoms, general well-being including any sleep disturbances, and quality of life on the Short Form 36 (SF-36) health survey. Participants also recorded use of any other medications during the 4-week study.

“I thought this was a very interesting study, as it proposes an alternative approach to manage patients with GERD,” Richa Shukla, MD, who was not affiliated with the research, said in an interview when asked to comment. “We see many patients with typical GERD symptoms who do not respond to PPI therapy, and perhaps considering an alternative cause and treatment may help with these patients.”

Dr. Shukla shared a couple of caveats. “This is a relatively small study, and it has not yet completed its enrollment target, so it will be helpful to see what the results are with the full study.” Also, it would be useful to know how many participants also took a PPI during the study, she said.

“Essentially, a lot remains unknown, but the study holds promise for patients,” added Dr. Shukla, assistant professor in the section of gastroenterology and hepatology at Baylor College of Medicine, Houston. “I think there is a lot of interest in the microbiome and how modulating it can impact inflammatory conditions.”
 

Key findings

The increase in heartburn-free days translated to more than eight additional days a month in which patients had no complaints of acid or heartburn. The difference from baseline was statistically significant (P < .001).

About two-thirds (66%) of participants were classified as “strong responders” to treatment, meaning they experienced an improvement of >50% in their ReQuest symptom scores over the 4 weeks. Again, the difference compared to baseline was statistically significant (P < .001).

The researchers also reported statistically significant improvements in quality-of-life indicators, such as well-being and sleep (P < .001).

The primary endpoint of the study was tolerability. The prebiotic was defined as tolerable if the ReQuest symptom scores and SF-36 scores remained constant or improved by the fourth week. ReQuest symptom scores improved for 89% of participants.

Two participants experienced nausea. No other adverse events related to ISOT-101 were reported. For five participants, ReQuest GI subscores worsened over time. For four participants, ReQuest total symptom scores worsened over time; that score represents a sum of GI and general well-being scores.
 

Unanswered questions

Inflammation in GERD is likely due to bacterial dysbiosis and acid-induced injury, Dr. Selling said.

If development of the prebiotic continues successfully, it could represent a paradigm shift in this clinical area, he said. “It suggests moving from acid reduction to also reducing dysbiosis as a treatment modality.”

But it remains unclear whether ISOT-101 would be indicated as monotherapy or for use in combination with other therapies for GERD.

Another unanswered question is whether the agent could be used to treat progressive disease. “This type of bacterial dysbiosis remains throughout the disease progression, from GERD to Barrett’s esophagus to esophageal adenocarcinoma,” Dr. Selling said.

The investigators reported that further controlled studies are forthcoming.

Dr. Selling is a co-founder and chief medical officer at ISOThrive. Dr. Shukla has disclosed no relevant financial relationships. David Johnson, MD, one of the authors of the abstract, is an advisor and contributor to Medscape.

A version of this article first appeared on Medscape.com.

A prebiotic therapy in development significantly reduced the number of days per month that people with gastroesophageal reflux disease (GERD) experienced heartburn.

The prebiotic treatment, maltosyl-isomalto-oligosaccharides (MIMO, ISOT-101), under development by ISOThrive, was also associated with reduced symptom severity and improved quality of life, John Selling, MD, chief medical officer at ISOThrive, said during the presentation of his study at the virtual Digestive Disease Week (DDW) 2021.

ISOT-101 is a nondigestible, nonabsorbable prebiotic carbohydrate produced by bacterial fermentation of sucrose and maltose. It was “possibly a staple of the bacterial diet that was present in the human diet during the past 10,000 years,” Dr. Selling said. He is a clinical associate professor of medicine and gastroenterology at Stanford (Calif.) University.

The prebiotic, however, “has been absent in our diet for about 50 to 100 years, driven by changes in agriculture, food production, food preservation, and dietary preferences,” he added.

Acid suppression treatments, such as proton pump inhibitors (PPIs), have long been a staple of treating GERD. However, about 40% of people taking PPIs still have symptoms, Dr. Selling said. He noted that there are concerns about the health risks associated with long-term PPI use.

A prebiotic could work because the distal esophageal microbiome in people with GERD “differs greatly” from that of healthy persons, Dr. Selling said. The prebiotic could help reduce an abnormal increase in gram-negative bacteria in these patients, for example. These bacterial strains express lipopolysaccharides on their outer cell membranes, which, in turn, alter cytokine signaling. This mechanism could lead to the hyperinflammatory state associated with GERD.

Dr. Selling and colleagues hypothesized that this treatment could help resolve GERD symptoms in two ways. The prebiotic could selectively feed the beneficial gram-positive bacteria in the distal esophagus, thereby helping to restore a healthy balance of bacteria. ISOT-101 could also produce bacteriocins that help kill the harmful gram-negative bacteria and control inflammation.

To assess the efficacy and tolerability of ISOT-101, Dr. Selling and colleagues plan to evaluate use of the agent in 110 people with GERD. The data presented at this year’s DDW are based on the first 44 participants to complete the study protocol.

Participants had to have active symptoms four or more days a week. They verbally reported symptoms to investigators and completed a daily ReQuest validated GERD symptom questionnaire.

After a week of baseline screening, participants consumed about a quarter teaspoon of ISOT-101 as the last substance swallowed before bed every night. The investigators asked participants to rate their GI symptoms, general well-being including any sleep disturbances, and quality of life on the Short Form 36 (SF-36) health survey. Participants also recorded use of any other medications during the 4-week study.

“I thought this was a very interesting study, as it proposes an alternative approach to manage patients with GERD,” Richa Shukla, MD, who was not affiliated with the research, said in an interview when asked to comment. “We see many patients with typical GERD symptoms who do not respond to PPI therapy, and perhaps considering an alternative cause and treatment may help with these patients.”

Dr. Shukla shared a couple of caveats. “This is a relatively small study, and it has not yet completed its enrollment target, so it will be helpful to see what the results are with the full study.” Also, it would be useful to know how many participants also took a PPI during the study, she said.

“Essentially, a lot remains unknown, but the study holds promise for patients,” added Dr. Shukla, assistant professor in the section of gastroenterology and hepatology at Baylor College of Medicine, Houston. “I think there is a lot of interest in the microbiome and how modulating it can impact inflammatory conditions.”
 

Key findings

The increase in heartburn-free days translated to more than eight additional days a month in which patients had no complaints of acid or heartburn. The difference from baseline was statistically significant (P < .001).

About two-thirds (66%) of participants were classified as “strong responders” to treatment, meaning they experienced an improvement of >50% in their ReQuest symptom scores over the 4 weeks. Again, the difference compared to baseline was statistically significant (P < .001).

The researchers also reported statistically significant improvements in quality-of-life indicators, such as well-being and sleep (P < .001).

The primary endpoint of the study was tolerability. The prebiotic was defined as tolerable if the ReQuest symptom scores and SF-36 scores remained constant or improved by the fourth week. ReQuest symptom scores improved for 89% of participants.

Two participants experienced nausea. No other adverse events related to ISOT-101 were reported. For five participants, ReQuest GI subscores worsened over time. For four participants, ReQuest total symptom scores worsened over time; that score represents a sum of GI and general well-being scores.
 

Unanswered questions

Inflammation in GERD is likely due to bacterial dysbiosis and acid-induced injury, Dr. Selling said.

If development of the prebiotic continues successfully, it could represent a paradigm shift in this clinical area, he said. “It suggests moving from acid reduction to also reducing dysbiosis as a treatment modality.”

But it remains unclear whether ISOT-101 would be indicated as monotherapy or for use in combination with other therapies for GERD.

Another unanswered question is whether the agent could be used to treat progressive disease. “This type of bacterial dysbiosis remains throughout the disease progression, from GERD to Barrett’s esophagus to esophageal adenocarcinoma,” Dr. Selling said.

The investigators reported that further controlled studies are forthcoming.

Dr. Selling is a co-founder and chief medical officer at ISOThrive. Dr. Shukla has disclosed no relevant financial relationships. David Johnson, MD, one of the authors of the abstract, is an advisor and contributor to Medscape.

A version of this article first appeared on Medscape.com.

A prebiotic therapy in development significantly reduced the number of days per month that people with gastroesophageal reflux disease (GERD) experienced heartburn.

The prebiotic treatment, maltosyl-isomalto-oligosaccharides (MIMO, ISOT-101), under development by ISOThrive, was also associated with reduced symptom severity and improved quality of life, John Selling, MD, chief medical officer at ISOThrive, said during the presentation of his study at the virtual Digestive Disease Week (DDW) 2021.

ISOT-101 is a nondigestible, nonabsorbable prebiotic carbohydrate produced by bacterial fermentation of sucrose and maltose. It was “possibly a staple of the bacterial diet that was present in the human diet during the past 10,000 years,” Dr. Selling said. He is a clinical associate professor of medicine and gastroenterology at Stanford (Calif.) University.

The prebiotic, however, “has been absent in our diet for about 50 to 100 years, driven by changes in agriculture, food production, food preservation, and dietary preferences,” he added.

Acid suppression treatments, such as proton pump inhibitors (PPIs), have long been a staple of treating GERD. However, about 40% of people taking PPIs still have symptoms, Dr. Selling said. He noted that there are concerns about the health risks associated with long-term PPI use.

A prebiotic could work because the distal esophageal microbiome in people with GERD “differs greatly” from that of healthy persons, Dr. Selling said. The prebiotic could help reduce an abnormal increase in gram-negative bacteria in these patients, for example. These bacterial strains express lipopolysaccharides on their outer cell membranes, which, in turn, alter cytokine signaling. This mechanism could lead to the hyperinflammatory state associated with GERD.

Dr. Selling and colleagues hypothesized that this treatment could help resolve GERD symptoms in two ways. The prebiotic could selectively feed the beneficial gram-positive bacteria in the distal esophagus, thereby helping to restore a healthy balance of bacteria. ISOT-101 could also produce bacteriocins that help kill the harmful gram-negative bacteria and control inflammation.

To assess the efficacy and tolerability of ISOT-101, Dr. Selling and colleagues plan to evaluate use of the agent in 110 people with GERD. The data presented at this year’s DDW are based on the first 44 participants to complete the study protocol.

Participants had to have active symptoms four or more days a week. They verbally reported symptoms to investigators and completed a daily ReQuest validated GERD symptom questionnaire.

After a week of baseline screening, participants consumed about a quarter teaspoon of ISOT-101 as the last substance swallowed before bed every night. The investigators asked participants to rate their GI symptoms, general well-being including any sleep disturbances, and quality of life on the Short Form 36 (SF-36) health survey. Participants also recorded use of any other medications during the 4-week study.

“I thought this was a very interesting study, as it proposes an alternative approach to manage patients with GERD,” Richa Shukla, MD, who was not affiliated with the research, said in an interview when asked to comment. “We see many patients with typical GERD symptoms who do not respond to PPI therapy, and perhaps considering an alternative cause and treatment may help with these patients.”

Dr. Shukla shared a couple of caveats. “This is a relatively small study, and it has not yet completed its enrollment target, so it will be helpful to see what the results are with the full study.” Also, it would be useful to know how many participants also took a PPI during the study, she said.

“Essentially, a lot remains unknown, but the study holds promise for patients,” added Dr. Shukla, assistant professor in the section of gastroenterology and hepatology at Baylor College of Medicine, Houston. “I think there is a lot of interest in the microbiome and how modulating it can impact inflammatory conditions.”
 

Key findings

The increase in heartburn-free days translated to more than eight additional days a month in which patients had no complaints of acid or heartburn. The difference from baseline was statistically significant (P < .001).

About two-thirds (66%) of participants were classified as “strong responders” to treatment, meaning they experienced an improvement of >50% in their ReQuest symptom scores over the 4 weeks. Again, the difference compared to baseline was statistically significant (P < .001).

The researchers also reported statistically significant improvements in quality-of-life indicators, such as well-being and sleep (P < .001).

The primary endpoint of the study was tolerability. The prebiotic was defined as tolerable if the ReQuest symptom scores and SF-36 scores remained constant or improved by the fourth week. ReQuest symptom scores improved for 89% of participants.

Two participants experienced nausea. No other adverse events related to ISOT-101 were reported. For five participants, ReQuest GI subscores worsened over time. For four participants, ReQuest total symptom scores worsened over time; that score represents a sum of GI and general well-being scores.
 

Unanswered questions

Inflammation in GERD is likely due to bacterial dysbiosis and acid-induced injury, Dr. Selling said.

If development of the prebiotic continues successfully, it could represent a paradigm shift in this clinical area, he said. “It suggests moving from acid reduction to also reducing dysbiosis as a treatment modality.”

But it remains unclear whether ISOT-101 would be indicated as monotherapy or for use in combination with other therapies for GERD.

Another unanswered question is whether the agent could be used to treat progressive disease. “This type of bacterial dysbiosis remains throughout the disease progression, from GERD to Barrett’s esophagus to esophageal adenocarcinoma,” Dr. Selling said.

The investigators reported that further controlled studies are forthcoming.

Dr. Selling is a co-founder and chief medical officer at ISOThrive. Dr. Shukla has disclosed no relevant financial relationships. David Johnson, MD, one of the authors of the abstract, is an advisor and contributor to Medscape.

A version of this article first appeared on Medscape.com.

A “smart toilet” in development uses artificial intelligence (AI) to scan stool for consistency and presence of blood – and early evidence suggests it is more accurate than patient self-reporting, a study reveals.

The remote, automated, real-time analysis and reporting increase the likelihood of physicians detecting gastrointestinal issues earlier, investigators reported.

In a proof-of-concept study, the smart toilet was 85% accurate in categorizing stool consistency as loose, normal, or constipated. The findings were presented at the annual Digestive Disease Week® (DDW).

“This study highlights a very innovative and practical tool that could have major implications for patients and clinicians alike,” Andrea Shin, MD, who was not affiliated with the research, said in an interview.

“Stool form or consistency and signs of bleeding are some of the most important pieces of clinical history when it comes to GI or bowel symptoms,” added Dr. Shin, assistant professor of medicine in the department of gastroenterology and hepatology at Indiana University, Indianapolis.
 

Image analysis

The researchers tested their AI algorithm on 3,328 images. They assessed photos from the Internet and some submitted anonymously by participants in the study.

Two gastroenterologists also rated a subset of 552 images. The physicians showed “satisfactory agreement” on interrater reliability (the extent to which two or more “raters” [for example, observers, examiners] agree), the investigators noted.

The smart toilet also was 76% accurate for gross blood detection.

“It’s objective and more accurate,” study author Sonia Grego, PhD, said in an interview. In contrast to asking patients to keep a bowel movement diary or recall the frequency and consistency of their stool over time, “the system does it for you,” she added.

“Our technology – by automating the image acquisition – removes the burden of having to track your pattern for weeks or months,” added Dr. Grego, founding director of the Duke Smart Toilet Lab at Duke University in Durham, N.C.

Information provided by patients “can have a big impact on decision-making,” Dr. Shin said. “For example, if I am talking to an individual who suffers from irritable bowel syndrome [IBS], I commonly ask them about how loose or watery and hard or formed their stool is, because this information gives me clues as to the underlying problems that may be driving their symptoms.”

Dr. Shin agreed it can be challenging for people to know what is important to report to their doctor. “This tool has the potential to relieve patient burden and facilitate communication between a patient and their clinician. It’s a great example of how technology can be leveraged to enhance care.”
 

Working behind the scenes

Together with gastroenterologist Deborah Anne Fisher, MD, an associate professor of medicine at Duke, Dr. Grego and colleagues devised a prototype that positions the image analyzer in the pipes behind the toilet. So the analysis is done post flush.

“We are experts of toilets and toilet technology,” Dr. Grego said. “We have learned that people really don’t like to see anything weird around the toilet bowl.”

The smart toilet system is designed for multiple users in a residential or commercial setting. The technology could be used in hospitals or long-term care facilities, for example. A fingerprint scanner on the flush mechanism tracks each individual user.
 

Mixed reactions

Dr. Grego gets a range of reactions when she tells people she is developing smart toilet technology.

“Friends and family laugh about the concept of the smart toilet,” she said, “so all the possible jokes that have been done on poops, we know.”

In fact, the researchers also are collecting the jokes they hear. “We’re being very systematic.”

In contrast, gastroenterologists who learn of the technology in development are more enthusiastic, Dr. Grego said. “There is such a need for removing the uncertainty of the patient recall about bowel movement frequency and appearance.

“We are seeking to expand through collaboration with additional GI doctors. We want to develop a more advanced prototype and do further validation studies,” Dr. Grego said.
 

Digital health tool

There is an aversion among patients to handling stool “or even talking about it,” Dr. Grego said. Colleagues tell her that people are more willing to provide a blood sample, which requires a needle, than a stool sample.

“But a lot of health data is there [in the stool],” she added. “We think this will empower a lot of research as well as consumer data gathering.”

For example, Dr. Grego envisions pharmaceutical companies using the technology to detect or monitor any changes in stool or gut health based on a treatment in development during clinical trials.

Furthermore, the technology might empower health-conscious consumers who want to track their own gut health. “This technology will be a whole new entry in the digital health toolkit,” Dr. Grego said.

Although not included in the research presented at this year’s DDW, the developers plan to add a sampling capability. Biochemic analysis of stool samples could provide “metabolically relevant information,” including stool biomarkers and microbiome composition.

“We have demonstrated it in the laboratory. It will be part of the technology when developed into a product,” Dr. Grego said.

This proof-of-concept study “is the first step in a path we are aggressively pursuing,” Dr. Grego said. She estimated it will take about 12-18 months to develop a prototype for use with patients. “We hope to move to a product soon after that.”

“I’m looking forward to seeing future iterations of this tool,” Dr. Shin said. “It could have a role in monitoring important GI diseases and disorders, including IBS and inflammatory bowel disease, or even for the detection of ‘alarm symptoms’ that shouldn’t be ignored.

“I could even see it having a role in preventative health in the future,” Dr. Shin added. 

The technology has been licensed to the spin-off company Coprata to develop the product further.

“We hope to have an impact on people’s health very soon,” Dr. Grego said.  

Duke University funded the study. Dr. Grego holds a management position at Coprata. Dr. Shin disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A “smart toilet” in development uses artificial intelligence (AI) to scan stool for consistency and presence of blood – and early evidence suggests it is more accurate than patient self-reporting, a study reveals.

The remote, automated, real-time analysis and reporting increase the likelihood of physicians detecting gastrointestinal issues earlier, investigators reported.

In a proof-of-concept study, the smart toilet was 85% accurate in categorizing stool consistency as loose, normal, or constipated. The findings were presented at the annual Digestive Disease Week® (DDW).

“This study highlights a very innovative and practical tool that could have major implications for patients and clinicians alike,” Andrea Shin, MD, who was not affiliated with the research, said in an interview.

“Stool form or consistency and signs of bleeding are some of the most important pieces of clinical history when it comes to GI or bowel symptoms,” added Dr. Shin, assistant professor of medicine in the department of gastroenterology and hepatology at Indiana University, Indianapolis.
 

Image analysis

The researchers tested their AI algorithm on 3,328 images. They assessed photos from the Internet and some submitted anonymously by participants in the study.

Two gastroenterologists also rated a subset of 552 images. The physicians showed “satisfactory agreement” on interrater reliability (the extent to which two or more “raters” [for example, observers, examiners] agree), the investigators noted.

The smart toilet also was 76% accurate for gross blood detection.

“It’s objective and more accurate,” study author Sonia Grego, PhD, said in an interview. In contrast to asking patients to keep a bowel movement diary or recall the frequency and consistency of their stool over time, “the system does it for you,” she added.

“Our technology – by automating the image acquisition – removes the burden of having to track your pattern for weeks or months,” added Dr. Grego, founding director of the Duke Smart Toilet Lab at Duke University in Durham, N.C.

Information provided by patients “can have a big impact on decision-making,” Dr. Shin said. “For example, if I am talking to an individual who suffers from irritable bowel syndrome [IBS], I commonly ask them about how loose or watery and hard or formed their stool is, because this information gives me clues as to the underlying problems that may be driving their symptoms.”

Dr. Shin agreed it can be challenging for people to know what is important to report to their doctor. “This tool has the potential to relieve patient burden and facilitate communication between a patient and their clinician. It’s a great example of how technology can be leveraged to enhance care.”
 

Working behind the scenes

Together with gastroenterologist Deborah Anne Fisher, MD, an associate professor of medicine at Duke, Dr. Grego and colleagues devised a prototype that positions the image analyzer in the pipes behind the toilet. So the analysis is done post flush.

“We are experts of toilets and toilet technology,” Dr. Grego said. “We have learned that people really don’t like to see anything weird around the toilet bowl.”

The smart toilet system is designed for multiple users in a residential or commercial setting. The technology could be used in hospitals or long-term care facilities, for example. A fingerprint scanner on the flush mechanism tracks each individual user.
 

Mixed reactions

Dr. Grego gets a range of reactions when she tells people she is developing smart toilet technology.

“Friends and family laugh about the concept of the smart toilet,” she said, “so all the possible jokes that have been done on poops, we know.”

In fact, the researchers also are collecting the jokes they hear. “We’re being very systematic.”

In contrast, gastroenterologists who learn of the technology in development are more enthusiastic, Dr. Grego said. “There is such a need for removing the uncertainty of the patient recall about bowel movement frequency and appearance.

“We are seeking to expand through collaboration with additional GI doctors. We want to develop a more advanced prototype and do further validation studies,” Dr. Grego said.
 

Digital health tool

There is an aversion among patients to handling stool “or even talking about it,” Dr. Grego said. Colleagues tell her that people are more willing to provide a blood sample, which requires a needle, than a stool sample.

“But a lot of health data is there [in the stool],” she added. “We think this will empower a lot of research as well as consumer data gathering.”

For example, Dr. Grego envisions pharmaceutical companies using the technology to detect or monitor any changes in stool or gut health based on a treatment in development during clinical trials.

Furthermore, the technology might empower health-conscious consumers who want to track their own gut health. “This technology will be a whole new entry in the digital health toolkit,” Dr. Grego said.

Although not included in the research presented at this year’s DDW, the developers plan to add a sampling capability. Biochemic analysis of stool samples could provide “metabolically relevant information,” including stool biomarkers and microbiome composition.

“We have demonstrated it in the laboratory. It will be part of the technology when developed into a product,” Dr. Grego said.

This proof-of-concept study “is the first step in a path we are aggressively pursuing,” Dr. Grego said. She estimated it will take about 12-18 months to develop a prototype for use with patients. “We hope to move to a product soon after that.”

“I’m looking forward to seeing future iterations of this tool,” Dr. Shin said. “It could have a role in monitoring important GI diseases and disorders, including IBS and inflammatory bowel disease, or even for the detection of ‘alarm symptoms’ that shouldn’t be ignored.

“I could even see it having a role in preventative health in the future,” Dr. Shin added. 

The technology has been licensed to the spin-off company Coprata to develop the product further.

“We hope to have an impact on people’s health very soon,” Dr. Grego said.  

Duke University funded the study. Dr. Grego holds a management position at Coprata. Dr. Shin disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A “smart toilet” in development uses artificial intelligence (AI) to scan stool for consistency and presence of blood – and early evidence suggests it is more accurate than patient self-reporting, a study reveals.

The remote, automated, real-time analysis and reporting increase the likelihood of physicians detecting gastrointestinal issues earlier, investigators reported.

In a proof-of-concept study, the smart toilet was 85% accurate in categorizing stool consistency as loose, normal, or constipated. The findings were presented at the annual Digestive Disease Week® (DDW).

“This study highlights a very innovative and practical tool that could have major implications for patients and clinicians alike,” Andrea Shin, MD, who was not affiliated with the research, said in an interview.

“Stool form or consistency and signs of bleeding are some of the most important pieces of clinical history when it comes to GI or bowel symptoms,” added Dr. Shin, assistant professor of medicine in the department of gastroenterology and hepatology at Indiana University, Indianapolis.
 

Image analysis

The researchers tested their AI algorithm on 3,328 images. They assessed photos from the Internet and some submitted anonymously by participants in the study.

Two gastroenterologists also rated a subset of 552 images. The physicians showed “satisfactory agreement” on interrater reliability (the extent to which two or more “raters” [for example, observers, examiners] agree), the investigators noted.

The smart toilet also was 76% accurate for gross blood detection.

“It’s objective and more accurate,” study author Sonia Grego, PhD, said in an interview. In contrast to asking patients to keep a bowel movement diary or recall the frequency and consistency of their stool over time, “the system does it for you,” she added.

“Our technology – by automating the image acquisition – removes the burden of having to track your pattern for weeks or months,” added Dr. Grego, founding director of the Duke Smart Toilet Lab at Duke University in Durham, N.C.

Information provided by patients “can have a big impact on decision-making,” Dr. Shin said. “For example, if I am talking to an individual who suffers from irritable bowel syndrome [IBS], I commonly ask them about how loose or watery and hard or formed their stool is, because this information gives me clues as to the underlying problems that may be driving their symptoms.”

Dr. Shin agreed it can be challenging for people to know what is important to report to their doctor. “This tool has the potential to relieve patient burden and facilitate communication between a patient and their clinician. It’s a great example of how technology can be leveraged to enhance care.”
 

Working behind the scenes

Together with gastroenterologist Deborah Anne Fisher, MD, an associate professor of medicine at Duke, Dr. Grego and colleagues devised a prototype that positions the image analyzer in the pipes behind the toilet. So the analysis is done post flush.

“We are experts of toilets and toilet technology,” Dr. Grego said. “We have learned that people really don’t like to see anything weird around the toilet bowl.”

The smart toilet system is designed for multiple users in a residential or commercial setting. The technology could be used in hospitals or long-term care facilities, for example. A fingerprint scanner on the flush mechanism tracks each individual user.
 

Mixed reactions

Dr. Grego gets a range of reactions when she tells people she is developing smart toilet technology.

“Friends and family laugh about the concept of the smart toilet,” she said, “so all the possible jokes that have been done on poops, we know.”

In fact, the researchers also are collecting the jokes they hear. “We’re being very systematic.”

In contrast, gastroenterologists who learn of the technology in development are more enthusiastic, Dr. Grego said. “There is such a need for removing the uncertainty of the patient recall about bowel movement frequency and appearance.

“We are seeking to expand through collaboration with additional GI doctors. We want to develop a more advanced prototype and do further validation studies,” Dr. Grego said.
 

Digital health tool

There is an aversion among patients to handling stool “or even talking about it,” Dr. Grego said. Colleagues tell her that people are more willing to provide a blood sample, which requires a needle, than a stool sample.

“But a lot of health data is there [in the stool],” she added. “We think this will empower a lot of research as well as consumer data gathering.”

For example, Dr. Grego envisions pharmaceutical companies using the technology to detect or monitor any changes in stool or gut health based on a treatment in development during clinical trials.

Furthermore, the technology might empower health-conscious consumers who want to track their own gut health. “This technology will be a whole new entry in the digital health toolkit,” Dr. Grego said.

Although not included in the research presented at this year’s DDW, the developers plan to add a sampling capability. Biochemic analysis of stool samples could provide “metabolically relevant information,” including stool biomarkers and microbiome composition.

“We have demonstrated it in the laboratory. It will be part of the technology when developed into a product,” Dr. Grego said.

This proof-of-concept study “is the first step in a path we are aggressively pursuing,” Dr. Grego said. She estimated it will take about 12-18 months to develop a prototype for use with patients. “We hope to move to a product soon after that.”

“I’m looking forward to seeing future iterations of this tool,” Dr. Shin said. “It could have a role in monitoring important GI diseases and disorders, including IBS and inflammatory bowel disease, or even for the detection of ‘alarm symptoms’ that shouldn’t be ignored.

“I could even see it having a role in preventative health in the future,” Dr. Shin added. 

The technology has been licensed to the spin-off company Coprata to develop the product further.

“We hope to have an impact on people’s health very soon,” Dr. Grego said.  

Duke University funded the study. Dr. Grego holds a management position at Coprata. Dr. Shin disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Combining minimally invasive endoscopic sleeve gastroplasty with a weekly injection of the glucagonlike peptide–1 agonist semaglutide (Ozempic, Novo Nordisk) leads to significantly greater weight loss than ESG alone in patients with diabetes and excess weight who are not candidates for bariatric surgery, new research shows.

During minimally invasive ESG, a flexible endoscope equipped with an endoscopic suturing device is inserted down the esophagus and into the stomach. The endoscopist then applies the sutures to the upper portion of the stomach, minimizing its size to restrict the amount of food a patient can ingest.

“Our stomachs can stretch back a bit, but we can use the suturing device again,” explained the lead investigator of the research Anna Carolina Hoff, MD, founder and clinical director of Angioskope Brazil in São José dos Campos.

“It’s important that patients with diabetes lose as much weight as possible because, if they lose about 10% of their total body weight, they have a great improvement in their glycemic levels, and some patients can even stop taking their [antidiabetic] medications,” Dr. Hoff said in an interview.

“And we found that by adding the GLP-1 agonist [semaglutide], we could increase weight loss from, on average, about 16%-18% of total body weight with ESG alone to up to 27%, so it’s a great metabolic combination,” she noted.

Dr. Hoff presented the findings at the annual Digestive Disease Week® (DDW).

Asked to comment, Scott Kahan, MD, MPH, director, National Center for Weight and Wellness, George Washington University, Washington, cautioned that it’s still early days for minimally invasive ESG.

“It is reasonable to assume that the long-term outcomes [with ESG] won’t be as good or durable over time as with bariatric surgery, but ... we will have to see.”

However, “we know that, typically, combinations of therapeutic options work better than a one-off option, so I think the real benefit of this study – outside the specific procedure and this specific medication – is that it is a very valuable proof-of-principle study showing that combinations do work better,” Dr. Kahan said in an interview.
 

Minimally invasive endoscopic sleeve gastroplasty

ESG is a surrogate for laparoscopic sleeve gastrectomy that can offer the benefits of such a procedure to those who don’t qualify for, or don’t wish to pursue, bariatric surgery. It can be performed at an earlier stage of disease, in those with a body mass index of 30 mg/kg², whereas generally people are not offered bariatric procedures unless they have a BMI of at least 35 with comorbidities or a BMI of at least 40 if they do not have comorbidities.

Subcutaneous semaglutide is already approved for the treatment of type 2 diabetes in adults at doses of up to 1 mg/week; higher doses are needed for weight loss. Novo Nordisk has been investigating higher doses for weight loss in the STEP trial program, which is now complete, and the company has submitted the data to the Food and Drug Administration and European Medicines Agency for an additional indication of adults with obesity (BMI ≥30) or who are overweight (BMI ≥27) and who have at least one weight-related comorbidity, as an adjunct to a reduced-calorie diet and increased physical activity, with a decision expected soon.

Novo Nordisk has also developed an oral form of semaglutide, which has been approved as a once-daily agent for type 2 diabetes (Rybelsus) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
 

Patients lost fat mass as well as excess weight

The Brazilian study involved 58 patients with obesity or overweight who also had diabetes and were undergoing minimally invasive ESG; they were further randomized to receive semaglutide or placebo.

The GLP-1 agonist (or sham placebo) was initiated 1 month after participants had undergone the procedure and patients were monitored each month for weight loss and type of fat loss achieved with the combination versus ESG alone. The initial dose of semaglutide used was 0.25 mg subcutaneous a week but could be titrated up to a maximum dose of 1.5 mg.

At the end of 11 months of active treatment versus placebo (12 months after ESG), patients who received additional semaglutide lost 86.3% of their excess body weight – the amount of weight patients needed to lose to reach normal BMI – compared with only 60.4% for ESG controls.

Specifically, the mean percentage total body weight loss at the end of 12 months was 25.2% for those in the combination group, compared with 18.6% for those treated with ESG alone (P < .001).

More importantly, patients in the combination group lost 12.6% of their body fat mass, compared with 9% for ESG controls, while mean A1c levels fell more in those treated with additional semaglutide compared with controls (P = .0394).

Indeed, five patients in the combination group reverted to a nondiabetic state and were able to discontinue antidiabetic medications altogether, Dr. Hoff noted.

“Our main goal is not just to lose weight but to lose body mass fat, which is very different from just losing weight,” she explained.

If patients lose weight but still maintain a high percentage of body fat mass, they have what she refers to as “sarcopenic obesity” because in this state patients have lost a lot of muscle mass but still have high levels of metabolically active visceral fat. Among many other inflammatory complexes, metabolically active visceral fat contains a large number of inflammasomes, and it is the latter that have been associated with obesity-related cancers. 

“Obesity is a progressive disease, so what we are trying to do here is buy time for patients so they do not progress to [bariatric] surgery, and this approach gives patients a chance to act earlier before obesity takes over and more metabolic consequences occur,” Dr. Hoff emphasized.

So, when combined with semaglutide, “we now have a minimally invasive procedure that can be just as successful [as surgery] and which can be made available to even more people looking to lose a significant amount of weight,” she concluded.

Dr. Hoff and Dr. Kahan have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Combining minimally invasive endoscopic sleeve gastroplasty with a weekly injection of the glucagonlike peptide–1 agonist semaglutide (Ozempic, Novo Nordisk) leads to significantly greater weight loss than ESG alone in patients with diabetes and excess weight who are not candidates for bariatric surgery, new research shows.

During minimally invasive ESG, a flexible endoscope equipped with an endoscopic suturing device is inserted down the esophagus and into the stomach. The endoscopist then applies the sutures to the upper portion of the stomach, minimizing its size to restrict the amount of food a patient can ingest.

“Our stomachs can stretch back a bit, but we can use the suturing device again,” explained the lead investigator of the research Anna Carolina Hoff, MD, founder and clinical director of Angioskope Brazil in São José dos Campos.

“It’s important that patients with diabetes lose as much weight as possible because, if they lose about 10% of their total body weight, they have a great improvement in their glycemic levels, and some patients can even stop taking their [antidiabetic] medications,” Dr. Hoff said in an interview.

“And we found that by adding the GLP-1 agonist [semaglutide], we could increase weight loss from, on average, about 16%-18% of total body weight with ESG alone to up to 27%, so it’s a great metabolic combination,” she noted.

Dr. Hoff presented the findings at the annual Digestive Disease Week® (DDW).

Asked to comment, Scott Kahan, MD, MPH, director, National Center for Weight and Wellness, George Washington University, Washington, cautioned that it’s still early days for minimally invasive ESG.

“It is reasonable to assume that the long-term outcomes [with ESG] won’t be as good or durable over time as with bariatric surgery, but ... we will have to see.”

However, “we know that, typically, combinations of therapeutic options work better than a one-off option, so I think the real benefit of this study – outside the specific procedure and this specific medication – is that it is a very valuable proof-of-principle study showing that combinations do work better,” Dr. Kahan said in an interview.
 

Minimally invasive endoscopic sleeve gastroplasty

ESG is a surrogate for laparoscopic sleeve gastrectomy that can offer the benefits of such a procedure to those who don’t qualify for, or don’t wish to pursue, bariatric surgery. It can be performed at an earlier stage of disease, in those with a body mass index of 30 mg/kg², whereas generally people are not offered bariatric procedures unless they have a BMI of at least 35 with comorbidities or a BMI of at least 40 if they do not have comorbidities.

Subcutaneous semaglutide is already approved for the treatment of type 2 diabetes in adults at doses of up to 1 mg/week; higher doses are needed for weight loss. Novo Nordisk has been investigating higher doses for weight loss in the STEP trial program, which is now complete, and the company has submitted the data to the Food and Drug Administration and European Medicines Agency for an additional indication of adults with obesity (BMI ≥30) or who are overweight (BMI ≥27) and who have at least one weight-related comorbidity, as an adjunct to a reduced-calorie diet and increased physical activity, with a decision expected soon.

Novo Nordisk has also developed an oral form of semaglutide, which has been approved as a once-daily agent for type 2 diabetes (Rybelsus) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
 

Patients lost fat mass as well as excess weight

The Brazilian study involved 58 patients with obesity or overweight who also had diabetes and were undergoing minimally invasive ESG; they were further randomized to receive semaglutide or placebo.

The GLP-1 agonist (or sham placebo) was initiated 1 month after participants had undergone the procedure and patients were monitored each month for weight loss and type of fat loss achieved with the combination versus ESG alone. The initial dose of semaglutide used was 0.25 mg subcutaneous a week but could be titrated up to a maximum dose of 1.5 mg.

At the end of 11 months of active treatment versus placebo (12 months after ESG), patients who received additional semaglutide lost 86.3% of their excess body weight – the amount of weight patients needed to lose to reach normal BMI – compared with only 60.4% for ESG controls.

Specifically, the mean percentage total body weight loss at the end of 12 months was 25.2% for those in the combination group, compared with 18.6% for those treated with ESG alone (P < .001).

More importantly, patients in the combination group lost 12.6% of their body fat mass, compared with 9% for ESG controls, while mean A1c levels fell more in those treated with additional semaglutide compared with controls (P = .0394).

Indeed, five patients in the combination group reverted to a nondiabetic state and were able to discontinue antidiabetic medications altogether, Dr. Hoff noted.

“Our main goal is not just to lose weight but to lose body mass fat, which is very different from just losing weight,” she explained.

If patients lose weight but still maintain a high percentage of body fat mass, they have what she refers to as “sarcopenic obesity” because in this state patients have lost a lot of muscle mass but still have high levels of metabolically active visceral fat. Among many other inflammatory complexes, metabolically active visceral fat contains a large number of inflammasomes, and it is the latter that have been associated with obesity-related cancers. 

“Obesity is a progressive disease, so what we are trying to do here is buy time for patients so they do not progress to [bariatric] surgery, and this approach gives patients a chance to act earlier before obesity takes over and more metabolic consequences occur,” Dr. Hoff emphasized.

So, when combined with semaglutide, “we now have a minimally invasive procedure that can be just as successful [as surgery] and which can be made available to even more people looking to lose a significant amount of weight,” she concluded.

Dr. Hoff and Dr. Kahan have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Combining minimally invasive endoscopic sleeve gastroplasty with a weekly injection of the glucagonlike peptide–1 agonist semaglutide (Ozempic, Novo Nordisk) leads to significantly greater weight loss than ESG alone in patients with diabetes and excess weight who are not candidates for bariatric surgery, new research shows.

During minimally invasive ESG, a flexible endoscope equipped with an endoscopic suturing device is inserted down the esophagus and into the stomach. The endoscopist then applies the sutures to the upper portion of the stomach, minimizing its size to restrict the amount of food a patient can ingest.

“Our stomachs can stretch back a bit, but we can use the suturing device again,” explained the lead investigator of the research Anna Carolina Hoff, MD, founder and clinical director of Angioskope Brazil in São José dos Campos.

“It’s important that patients with diabetes lose as much weight as possible because, if they lose about 10% of their total body weight, they have a great improvement in their glycemic levels, and some patients can even stop taking their [antidiabetic] medications,” Dr. Hoff said in an interview.

“And we found that by adding the GLP-1 agonist [semaglutide], we could increase weight loss from, on average, about 16%-18% of total body weight with ESG alone to up to 27%, so it’s a great metabolic combination,” she noted.

Dr. Hoff presented the findings at the annual Digestive Disease Week® (DDW).

Asked to comment, Scott Kahan, MD, MPH, director, National Center for Weight and Wellness, George Washington University, Washington, cautioned that it’s still early days for minimally invasive ESG.

“It is reasonable to assume that the long-term outcomes [with ESG] won’t be as good or durable over time as with bariatric surgery, but ... we will have to see.”

However, “we know that, typically, combinations of therapeutic options work better than a one-off option, so I think the real benefit of this study – outside the specific procedure and this specific medication – is that it is a very valuable proof-of-principle study showing that combinations do work better,” Dr. Kahan said in an interview.
 

Minimally invasive endoscopic sleeve gastroplasty

ESG is a surrogate for laparoscopic sleeve gastrectomy that can offer the benefits of such a procedure to those who don’t qualify for, or don’t wish to pursue, bariatric surgery. It can be performed at an earlier stage of disease, in those with a body mass index of 30 mg/kg², whereas generally people are not offered bariatric procedures unless they have a BMI of at least 35 with comorbidities or a BMI of at least 40 if they do not have comorbidities.

Subcutaneous semaglutide is already approved for the treatment of type 2 diabetes in adults at doses of up to 1 mg/week; higher doses are needed for weight loss. Novo Nordisk has been investigating higher doses for weight loss in the STEP trial program, which is now complete, and the company has submitted the data to the Food and Drug Administration and European Medicines Agency for an additional indication of adults with obesity (BMI ≥30) or who are overweight (BMI ≥27) and who have at least one weight-related comorbidity, as an adjunct to a reduced-calorie diet and increased physical activity, with a decision expected soon.

Novo Nordisk has also developed an oral form of semaglutide, which has been approved as a once-daily agent for type 2 diabetes (Rybelsus) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
 

Patients lost fat mass as well as excess weight

The Brazilian study involved 58 patients with obesity or overweight who also had diabetes and were undergoing minimally invasive ESG; they were further randomized to receive semaglutide or placebo.

The GLP-1 agonist (or sham placebo) was initiated 1 month after participants had undergone the procedure and patients were monitored each month for weight loss and type of fat loss achieved with the combination versus ESG alone. The initial dose of semaglutide used was 0.25 mg subcutaneous a week but could be titrated up to a maximum dose of 1.5 mg.

At the end of 11 months of active treatment versus placebo (12 months after ESG), patients who received additional semaglutide lost 86.3% of their excess body weight – the amount of weight patients needed to lose to reach normal BMI – compared with only 60.4% for ESG controls.

Specifically, the mean percentage total body weight loss at the end of 12 months was 25.2% for those in the combination group, compared with 18.6% for those treated with ESG alone (P < .001).

More importantly, patients in the combination group lost 12.6% of their body fat mass, compared with 9% for ESG controls, while mean A1c levels fell more in those treated with additional semaglutide compared with controls (P = .0394).

Indeed, five patients in the combination group reverted to a nondiabetic state and were able to discontinue antidiabetic medications altogether, Dr. Hoff noted.

“Our main goal is not just to lose weight but to lose body mass fat, which is very different from just losing weight,” she explained.

If patients lose weight but still maintain a high percentage of body fat mass, they have what she refers to as “sarcopenic obesity” because in this state patients have lost a lot of muscle mass but still have high levels of metabolically active visceral fat. Among many other inflammatory complexes, metabolically active visceral fat contains a large number of inflammasomes, and it is the latter that have been associated with obesity-related cancers. 

“Obesity is a progressive disease, so what we are trying to do here is buy time for patients so they do not progress to [bariatric] surgery, and this approach gives patients a chance to act earlier before obesity takes over and more metabolic consequences occur,” Dr. Hoff emphasized.

So, when combined with semaglutide, “we now have a minimally invasive procedure that can be just as successful [as surgery] and which can be made available to even more people looking to lose a significant amount of weight,” she concluded.

Dr. Hoff and Dr. Kahan have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Compared with placebo, sporebiotics significantly reduced postprandial distress, epigastric pain, and several other symptoms of functional dyspepsia, reported lead author Lucas Wauters, MD, PhD, of University Hospitals Leuven (Belgium), and colleagues.

“Acid suppressive or first-line therapy with PPIs [proton pump inhibitors] for functional dyspepsia has limited efficacy and potential long-term side effects,” the investigators reported at the annual Digestive Disease Week® (DDW). “Spore-forming bacteria or sporebiotics may be effective for postprandial distress and epigastric pain or burning symptoms, offering benefits which may differ in relation to PPI intake.”
 

Sporebiotics improve variety of symptoms

To test this hypothesis, the investigators recruited 68 patients with functional dyspepsia who had similar characteristics at baseline. Half of the participants (n = 34) were taking PPIs.

Patients were randomized in a 1:1 ratio to receive 2.5 x 10⁹ CFU of Bacillus coagulans MY01 and B. subtilis MY02 twice daily for 8 weeks, or matching placebo. Following this period, an additional 8-week open-label regimen was instituted, during which time all patients received sporebiotics. Throughout the study, a daily diary was used to self-report symptoms.

The primary outcome, measured at 8 weeks, was clinical response, defined by a decrease in weekly postprandial distress symptoms greater than 0.7 among patients who had a baseline score greater than 1.0. Secondary outcomes included change in postprandial distress symptoms greater than 0.5 (minimal clinical response), as well as changes in cardinal epigastric pain, cardinal postprandial distress, and other symptoms. At baseline and 8 weeks, patients taking PPIs underwent a ¹⁴C-glycocolic acid breath test to detect changes in small intestinal bacterial overgrowth.

At 8 weeks, a clinical response was observed in 48% of patients taking sporebiotics, compared with 20% of those in the placebo group (P = .03). At the same time point, 56% of patients in the treatment group had a minimal clinical response versus 27% in the control group (P = .03).

Spore-forming probiotics were also associated with significantly greater improvements in cardinal postprandial distress, cardinal epigastric pain, postprandial fullness, and upper abdominal pain. A trend toward improvement in upper abdominal bloating was also seen (P = .07).

Among patients taking PPIs, baseline rates of positivity for bile acid breath testing were similar between those in the sporebiotic and placebo group, at 18% and 25%, respectively (P = .29). After 8 weeks, however, patients taking spore-forming probiotics had a significantly lower rate of bile acid breath test positivity (7% vs. 36%; P = .04), suggesting improvements in small intestinal bacterial overgrowth.

In the open-label portion of the trial, patients in the treatment group maintained improvements in postprandial distress. Patients who switched from placebo to sporebiotics had a significant reduction in postprandial distress symptoms.

At 8 weeks, sporebiotics were associated with a trend toward fewer side effects of any kind (16% vs. 33%; P = .09), while rates of GI-specific side effects were comparable between groups, at 3% and 15% for sporebiotics and placebo, respectively (P = .2).“Spore-forming probiotics are effective and safe in patients with functional dyspepsia, decreasing both postprandial distress and epigastric pain symptoms,” the investigators concluded. “In patients [taking PPIs], sporebiotics decrease the percentage of positive bile acid breath tests, suggesting a reduction of small intestinal bacterial overgrowth.”

Results are promising, but big questions remain

Pankaj Jay Pasricha, MBBS, MD, vice chair of medicine innovation and commercialization at Johns Hopkins and director of the Johns Hopkins Center for Neurogastroenterology, Baltimore, called the results “very encouraging.”

“This [study] is the first of its kind for this condition,” Dr. Pasricha said in an interview. “It will be very interesting to see whether others can reproduce these findings, and whether [these improvements] are sustained beyond the first few weeks or months.”

He noted that determining associated mechanisms of action could potentially open up new lines of therapy, and provide greater understanding of pathophysiology, which is currently lacking.

“We don’t fully understand the pathophysiology [of functional dyspepsia],” Dr. Pasricha said. “If you don’t understand the pathophysiology, then it’s difficult to identify the right molecular target to address the root cause. Instead, we use a variety of symptomatic treatments that aren’t actually addressing the root cause, but studies like this may help us gain some insight into the cause of the problem, and if it is in fact a fundamental imbalance in the intestinal microbiota, then this would be a rational approach.”

It’s unclear how sporebiotics may improve functional dyspepsia, Dr. Pasricha noted. He proposed three possible mechanisms: the bacteria could be colonizing the intestine, they could be releasing products as they pass through the intestine that have a therapeutic effect, or they may be altering bile acid metabolism in the colon or having some other effect there.

“It’s speculative on my part to say how it works,” Dr. Pasricha said. “All the dots remain to be connected. But it’s a good start, and an outstanding group of investigators.”Dr. Wauters and colleagues reported no conflicts of interest. Dr. Pasricha disclosed a relationship with Pendulum Therapeutics.

Compared with placebo, sporebiotics significantly reduced postprandial distress, epigastric pain, and several other symptoms of functional dyspepsia, reported lead author Lucas Wauters, MD, PhD, of University Hospitals Leuven (Belgium), and colleagues.

“Acid suppressive or first-line therapy with PPIs [proton pump inhibitors] for functional dyspepsia has limited efficacy and potential long-term side effects,” the investigators reported at the annual Digestive Disease Week® (DDW). “Spore-forming bacteria or sporebiotics may be effective for postprandial distress and epigastric pain or burning symptoms, offering benefits which may differ in relation to PPI intake.”
 

Sporebiotics improve variety of symptoms

To test this hypothesis, the investigators recruited 68 patients with functional dyspepsia who had similar characteristics at baseline. Half of the participants (n = 34) were taking PPIs.

Patients were randomized in a 1:1 ratio to receive 2.5 x 10⁹ CFU of Bacillus coagulans MY01 and B. subtilis MY02 twice daily for 8 weeks, or matching placebo. Following this period, an additional 8-week open-label regimen was instituted, during which time all patients received sporebiotics. Throughout the study, a daily diary was used to self-report symptoms.

The primary outcome, measured at 8 weeks, was clinical response, defined by a decrease in weekly postprandial distress symptoms greater than 0.7 among patients who had a baseline score greater than 1.0. Secondary outcomes included change in postprandial distress symptoms greater than 0.5 (minimal clinical response), as well as changes in cardinal epigastric pain, cardinal postprandial distress, and other symptoms. At baseline and 8 weeks, patients taking PPIs underwent a ¹⁴C-glycocolic acid breath test to detect changes in small intestinal bacterial overgrowth.

At 8 weeks, a clinical response was observed in 48% of patients taking sporebiotics, compared with 20% of those in the placebo group (P = .03). At the same time point, 56% of patients in the treatment group had a minimal clinical response versus 27% in the control group (P = .03).

Spore-forming probiotics were also associated with significantly greater improvements in cardinal postprandial distress, cardinal epigastric pain, postprandial fullness, and upper abdominal pain. A trend toward improvement in upper abdominal bloating was also seen (P = .07).

Among patients taking PPIs, baseline rates of positivity for bile acid breath testing were similar between those in the sporebiotic and placebo group, at 18% and 25%, respectively (P = .29). After 8 weeks, however, patients taking spore-forming probiotics had a significantly lower rate of bile acid breath test positivity (7% vs. 36%; P = .04), suggesting improvements in small intestinal bacterial overgrowth.

In the open-label portion of the trial, patients in the treatment group maintained improvements in postprandial distress. Patients who switched from placebo to sporebiotics had a significant reduction in postprandial distress symptoms.

At 8 weeks, sporebiotics were associated with a trend toward fewer side effects of any kind (16% vs. 33%; P = .09), while rates of GI-specific side effects were comparable between groups, at 3% and 15% for sporebiotics and placebo, respectively (P = .2).“Spore-forming probiotics are effective and safe in patients with functional dyspepsia, decreasing both postprandial distress and epigastric pain symptoms,” the investigators concluded. “In patients [taking PPIs], sporebiotics decrease the percentage of positive bile acid breath tests, suggesting a reduction of small intestinal bacterial overgrowth.”

Results are promising, but big questions remain

Pankaj Jay Pasricha, MBBS, MD, vice chair of medicine innovation and commercialization at Johns Hopkins and director of the Johns Hopkins Center for Neurogastroenterology, Baltimore, called the results “very encouraging.”

“This [study] is the first of its kind for this condition,” Dr. Pasricha said in an interview. “It will be very interesting to see whether others can reproduce these findings, and whether [these improvements] are sustained beyond the first few weeks or months.”

He noted that determining associated mechanisms of action could potentially open up new lines of therapy, and provide greater understanding of pathophysiology, which is currently lacking.

“We don’t fully understand the pathophysiology [of functional dyspepsia],” Dr. Pasricha said. “If you don’t understand the pathophysiology, then it’s difficult to identify the right molecular target to address the root cause. Instead, we use a variety of symptomatic treatments that aren’t actually addressing the root cause, but studies like this may help us gain some insight into the cause of the problem, and if it is in fact a fundamental imbalance in the intestinal microbiota, then this would be a rational approach.”

It’s unclear how sporebiotics may improve functional dyspepsia, Dr. Pasricha noted. He proposed three possible mechanisms: the bacteria could be colonizing the intestine, they could be releasing products as they pass through the intestine that have a therapeutic effect, or they may be altering bile acid metabolism in the colon or having some other effect there.

“It’s speculative on my part to say how it works,” Dr. Pasricha said. “All the dots remain to be connected. But it’s a good start, and an outstanding group of investigators.”Dr. Wauters and colleagues reported no conflicts of interest. Dr. Pasricha disclosed a relationship with Pendulum Therapeutics.

Compared with placebo, sporebiotics significantly reduced postprandial distress, epigastric pain, and several other symptoms of functional dyspepsia, reported lead author Lucas Wauters, MD, PhD, of University Hospitals Leuven (Belgium), and colleagues.

“Acid suppressive or first-line therapy with PPIs [proton pump inhibitors] for functional dyspepsia has limited efficacy and potential long-term side effects,” the investigators reported at the annual Digestive Disease Week® (DDW). “Spore-forming bacteria or sporebiotics may be effective for postprandial distress and epigastric pain or burning symptoms, offering benefits which may differ in relation to PPI intake.”
 

Sporebiotics improve variety of symptoms

To test this hypothesis, the investigators recruited 68 patients with functional dyspepsia who had similar characteristics at baseline. Half of the participants (n = 34) were taking PPIs.

Patients were randomized in a 1:1 ratio to receive 2.5 x 10⁹ CFU of Bacillus coagulans MY01 and B. subtilis MY02 twice daily for 8 weeks, or matching placebo. Following this period, an additional 8-week open-label regimen was instituted, during which time all patients received sporebiotics. Throughout the study, a daily diary was used to self-report symptoms.

The primary outcome, measured at 8 weeks, was clinical response, defined by a decrease in weekly postprandial distress symptoms greater than 0.7 among patients who had a baseline score greater than 1.0. Secondary outcomes included change in postprandial distress symptoms greater than 0.5 (minimal clinical response), as well as changes in cardinal epigastric pain, cardinal postprandial distress, and other symptoms. At baseline and 8 weeks, patients taking PPIs underwent a ¹⁴C-glycocolic acid breath test to detect changes in small intestinal bacterial overgrowth.

At 8 weeks, a clinical response was observed in 48% of patients taking sporebiotics, compared with 20% of those in the placebo group (P = .03). At the same time point, 56% of patients in the treatment group had a minimal clinical response versus 27% in the control group (P = .03).

Spore-forming probiotics were also associated with significantly greater improvements in cardinal postprandial distress, cardinal epigastric pain, postprandial fullness, and upper abdominal pain. A trend toward improvement in upper abdominal bloating was also seen (P = .07).

Among patients taking PPIs, baseline rates of positivity for bile acid breath testing were similar between those in the sporebiotic and placebo group, at 18% and 25%, respectively (P = .29). After 8 weeks, however, patients taking spore-forming probiotics had a significantly lower rate of bile acid breath test positivity (7% vs. 36%; P = .04), suggesting improvements in small intestinal bacterial overgrowth.

In the open-label portion of the trial, patients in the treatment group maintained improvements in postprandial distress. Patients who switched from placebo to sporebiotics had a significant reduction in postprandial distress symptoms.

At 8 weeks, sporebiotics were associated with a trend toward fewer side effects of any kind (16% vs. 33%; P = .09), while rates of GI-specific side effects were comparable between groups, at 3% and 15% for sporebiotics and placebo, respectively (P = .2).“Spore-forming probiotics are effective and safe in patients with functional dyspepsia, decreasing both postprandial distress and epigastric pain symptoms,” the investigators concluded. “In patients [taking PPIs], sporebiotics decrease the percentage of positive bile acid breath tests, suggesting a reduction of small intestinal bacterial overgrowth.”

Results are promising, but big questions remain

Pankaj Jay Pasricha, MBBS, MD, vice chair of medicine innovation and commercialization at Johns Hopkins and director of the Johns Hopkins Center for Neurogastroenterology, Baltimore, called the results “very encouraging.”

“This [study] is the first of its kind for this condition,” Dr. Pasricha said in an interview. “It will be very interesting to see whether others can reproduce these findings, and whether [these improvements] are sustained beyond the first few weeks or months.”

He noted that determining associated mechanisms of action could potentially open up new lines of therapy, and provide greater understanding of pathophysiology, which is currently lacking.

“We don’t fully understand the pathophysiology [of functional dyspepsia],” Dr. Pasricha said. “If you don’t understand the pathophysiology, then it’s difficult to identify the right molecular target to address the root cause. Instead, we use a variety of symptomatic treatments that aren’t actually addressing the root cause, but studies like this may help us gain some insight into the cause of the problem, and if it is in fact a fundamental imbalance in the intestinal microbiota, then this would be a rational approach.”

It’s unclear how sporebiotics may improve functional dyspepsia, Dr. Pasricha noted. He proposed three possible mechanisms: the bacteria could be colonizing the intestine, they could be releasing products as they pass through the intestine that have a therapeutic effect, or they may be altering bile acid metabolism in the colon or having some other effect there.

“It’s speculative on my part to say how it works,” Dr. Pasricha said. “All the dots remain to be connected. But it’s a good start, and an outstanding group of investigators.”Dr. Wauters and colleagues reported no conflicts of interest. Dr. Pasricha disclosed a relationship with Pendulum Therapeutics.

Nasogastric intubation for esophageal manometry or impedance monitoring does not generate significant aerosol particles and is associated with minimal droplet spread, according to a Belgian study presented at the annual Digestive Disease Week® (DDW). These findings suggest that standard personal protective equipment and appropriate patient positioning are likely sufficient to protect health care workers from increased risk of coronavirus transmission during tube placement and removal, reported lead author Wout Verbeure, PhD, of Leuven University Hospital, Belgium, and colleagues.

“Subsequent to the COVID-19 peak, [nasogastric tube insertion and extraction] were scaled back based on the assumption that they generate respiratory aerosol particles and droplet spread,” the investigators reported. “However, there is no scientific evidence for this theory.”

To address this knowledge gap, the investigators conducted an observational trial involving SARS-CoV-2-negative patients and including 21 insertions and removals for high-resolution manometry (HRM), plus 12 insertions and 10 removals for 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH). During the study, a Camfil City M Air Purifier was added to the examination room. This was present during 13 of the 21 HRM insertions and removals, allowing for comparison of aerosol particle measurements before and after introduction of the device.
 

The mechanics of the study

Aerosol particles (0.3-10 mcm) were measured with a Particle Measuring Systems LASAIR II Particle Counter positioned 1 cm away from the patient’s face. For both procedures, measurements were taken before, during, and up to 5 minutes after each nasogastric tube placement and removal. Additional measurements were taken while the HRM examination was being conducted.

To measure droplet spread, 1% medical fluorescein in saline was applied to each patient’s nasal cavity; droplets were visualized on a white sheet covering the patient and a white apron worn by the health care worker. The patients’ masks were kept below their noses but were covering their mouths.

“During the placement and removal of the catheter, the health care worker was always standing sideways or even behind the patient, and they always stood higher relative to the patient to ensure that when there was aerosol or droplet spread, it was not in their direction,” Dr. Verbeure said during his virtual presentation.

During placement for HRM and removal for MII-pH, aerosol particles (excluding those that were 0.3 mcm), decreased significantly. Otherwise, particle counts remained stable. “This shows that these investigations do not generate additional aerosol [particles], which is good news,” Dr. Verbeure said.

When the air purifier was present, placement and examination for HRM were associated with significant reductions in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm), whereas removal caused a slight uptick in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm) that did not decline after 5 minutes. “This was actually a surprise to us,” Dr. Verbeure said. “Because we now had an air purifier present, and we expected an even lower number of particles.”

He suggested that the purifier may have been reducing particle counts during HRM examination, thereby lowering baseline values before removal, making small changes more noticeable; or the purifier may have been causing turbulence that spread particles during removal. Whether either of these hypotheses is true, Dr. Verbeure noted that particle counts were never higher than at the start of the examination. Fluorescein visualization showed “surprisingly little droplet spread,” Dr. Verbeure said, apart from some contamination around the patient’s neck.

“Esophageal investigations do not seem to generate additional [aerosol] particles,” Dr. Verbeure concluded. “So wearing the recommended protective gear and also considering the right positioning of the health care worker relative to the patient is important to keep performing this daily clinical routine.” To avoid droplet spread, health care workers should “be aware of the [patient’s] neck region and the direction of the catheter,” Dr. Verbeure added.
 

SORTing the results

According to Mahdi Najafi, MD, associate professor in the department of anesthesiology at Tehran University of Medical Sciences, Iran, and adjunct professor at Schulich School of Medicine & Dentistry, Western University, London, Ontario, the findings offer valuable insights. “[This study] is very important for at least two reasons: The extent of using this procedure in patient care, especially in the critical care setting, and the paucity of information for COVID-19 transmission and route of transmission as well,” Dr. Najafi said in an interview.

Yet he cautioned against generalizing the results. “We cannot extend the results to all nasogastric tube intubations,” Dr. Najafi said. “There are reasons for that. The tube for manometry is delicate and flexible, while the nasogastric tube used for drainage and GI pressure release – which is used commonly in intensive care and the operating room – is larger and rather rigid. Moreover, the patient is awake and conscious for manometry while the other procedures are done in sedated or unconscious patients.”

He noted that nasogastric intubation is more challenging in unconscious patients, and often requires a laryngoscope and/or Magill forceps. “The result [of using these instruments] is coughing, which is undoubtedly the most important cause of aerosol generation,” Dr. Najafi said. “It can be regarded as a drawback to this study as well. The authors would be better to report the number and/or severity of the airway reactions during the procedures, which are the main source of droplets and aerosols.”

To reduce risk of coronavirus transmission during nasogastric intubation of unconscious patients, Dr. Najafi recommended the SORT (Sniffing position, nasogastric tube Orientation, contralateral Rotation, and Twisting movement) maneuver, which he introduced in 2016 for use in critical care and operating room settings.

“The employment of anatomical approach and avoiding equipment for intubation were devised to increase the level of safety and decrease hazards and adverse effects,” Dr. Najafi said of the SORT maneuver. “The procedure needs to be done step-by-step and as smooth as possible.”

In a recent study, the SORT maneuver was compared with nasogastric intubation using neck flexion lateral pressure in critically ill patients. The investigators concluded that the SORT maneuver is “a promising method” notable for its simple technique, and suggested that more trials are needed.

The investigators and Dr. Najafi reported no conflicts of interest.

Nasogastric intubation for esophageal manometry or impedance monitoring does not generate significant aerosol particles and is associated with minimal droplet spread, according to a Belgian study presented at the annual Digestive Disease Week® (DDW). These findings suggest that standard personal protective equipment and appropriate patient positioning are likely sufficient to protect health care workers from increased risk of coronavirus transmission during tube placement and removal, reported lead author Wout Verbeure, PhD, of Leuven University Hospital, Belgium, and colleagues.

“Subsequent to the COVID-19 peak, [nasogastric tube insertion and extraction] were scaled back based on the assumption that they generate respiratory aerosol particles and droplet spread,” the investigators reported. “However, there is no scientific evidence for this theory.”

To address this knowledge gap, the investigators conducted an observational trial involving SARS-CoV-2-negative patients and including 21 insertions and removals for high-resolution manometry (HRM), plus 12 insertions and 10 removals for 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH). During the study, a Camfil City M Air Purifier was added to the examination room. This was present during 13 of the 21 HRM insertions and removals, allowing for comparison of aerosol particle measurements before and after introduction of the device.
 

The mechanics of the study

Aerosol particles (0.3-10 mcm) were measured with a Particle Measuring Systems LASAIR II Particle Counter positioned 1 cm away from the patient’s face. For both procedures, measurements were taken before, during, and up to 5 minutes after each nasogastric tube placement and removal. Additional measurements were taken while the HRM examination was being conducted.

To measure droplet spread, 1% medical fluorescein in saline was applied to each patient’s nasal cavity; droplets were visualized on a white sheet covering the patient and a white apron worn by the health care worker. The patients’ masks were kept below their noses but were covering their mouths.

“During the placement and removal of the catheter, the health care worker was always standing sideways or even behind the patient, and they always stood higher relative to the patient to ensure that when there was aerosol or droplet spread, it was not in their direction,” Dr. Verbeure said during his virtual presentation.

During placement for HRM and removal for MII-pH, aerosol particles (excluding those that were 0.3 mcm), decreased significantly. Otherwise, particle counts remained stable. “This shows that these investigations do not generate additional aerosol [particles], which is good news,” Dr. Verbeure said.

When the air purifier was present, placement and examination for HRM were associated with significant reductions in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm), whereas removal caused a slight uptick in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm) that did not decline after 5 minutes. “This was actually a surprise to us,” Dr. Verbeure said. “Because we now had an air purifier present, and we expected an even lower number of particles.”

He suggested that the purifier may have been reducing particle counts during HRM examination, thereby lowering baseline values before removal, making small changes more noticeable; or the purifier may have been causing turbulence that spread particles during removal. Whether either of these hypotheses is true, Dr. Verbeure noted that particle counts were never higher than at the start of the examination. Fluorescein visualization showed “surprisingly little droplet spread,” Dr. Verbeure said, apart from some contamination around the patient’s neck.

“Esophageal investigations do not seem to generate additional [aerosol] particles,” Dr. Verbeure concluded. “So wearing the recommended protective gear and also considering the right positioning of the health care worker relative to the patient is important to keep performing this daily clinical routine.” To avoid droplet spread, health care workers should “be aware of the [patient’s] neck region and the direction of the catheter,” Dr. Verbeure added.
 

SORTing the results

According to Mahdi Najafi, MD, associate professor in the department of anesthesiology at Tehran University of Medical Sciences, Iran, and adjunct professor at Schulich School of Medicine & Dentistry, Western University, London, Ontario, the findings offer valuable insights. “[This study] is very important for at least two reasons: The extent of using this procedure in patient care, especially in the critical care setting, and the paucity of information for COVID-19 transmission and route of transmission as well,” Dr. Najafi said in an interview.

Yet he cautioned against generalizing the results. “We cannot extend the results to all nasogastric tube intubations,” Dr. Najafi said. “There are reasons for that. The tube for manometry is delicate and flexible, while the nasogastric tube used for drainage and GI pressure release – which is used commonly in intensive care and the operating room – is larger and rather rigid. Moreover, the patient is awake and conscious for manometry while the other procedures are done in sedated or unconscious patients.”

He noted that nasogastric intubation is more challenging in unconscious patients, and often requires a laryngoscope and/or Magill forceps. “The result [of using these instruments] is coughing, which is undoubtedly the most important cause of aerosol generation,” Dr. Najafi said. “It can be regarded as a drawback to this study as well. The authors would be better to report the number and/or severity of the airway reactions during the procedures, which are the main source of droplets and aerosols.”

To reduce risk of coronavirus transmission during nasogastric intubation of unconscious patients, Dr. Najafi recommended the SORT (Sniffing position, nasogastric tube Orientation, contralateral Rotation, and Twisting movement) maneuver, which he introduced in 2016 for use in critical care and operating room settings.

“The employment of anatomical approach and avoiding equipment for intubation were devised to increase the level of safety and decrease hazards and adverse effects,” Dr. Najafi said of the SORT maneuver. “The procedure needs to be done step-by-step and as smooth as possible.”

In a recent study, the SORT maneuver was compared with nasogastric intubation using neck flexion lateral pressure in critically ill patients. The investigators concluded that the SORT maneuver is “a promising method” notable for its simple technique, and suggested that more trials are needed.

The investigators and Dr. Najafi reported no conflicts of interest.

Nasogastric intubation for esophageal manometry or impedance monitoring does not generate significant aerosol particles and is associated with minimal droplet spread, according to a Belgian study presented at the annual Digestive Disease Week® (DDW). These findings suggest that standard personal protective equipment and appropriate patient positioning are likely sufficient to protect health care workers from increased risk of coronavirus transmission during tube placement and removal, reported lead author Wout Verbeure, PhD, of Leuven University Hospital, Belgium, and colleagues.

“Subsequent to the COVID-19 peak, [nasogastric tube insertion and extraction] were scaled back based on the assumption that they generate respiratory aerosol particles and droplet spread,” the investigators reported. “However, there is no scientific evidence for this theory.”

To address this knowledge gap, the investigators conducted an observational trial involving SARS-CoV-2-negative patients and including 21 insertions and removals for high-resolution manometry (HRM), plus 12 insertions and 10 removals for 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH). During the study, a Camfil City M Air Purifier was added to the examination room. This was present during 13 of the 21 HRM insertions and removals, allowing for comparison of aerosol particle measurements before and after introduction of the device.
 

The mechanics of the study

Aerosol particles (0.3-10 mcm) were measured with a Particle Measuring Systems LASAIR II Particle Counter positioned 1 cm away from the patient’s face. For both procedures, measurements were taken before, during, and up to 5 minutes after each nasogastric tube placement and removal. Additional measurements were taken while the HRM examination was being conducted.

To measure droplet spread, 1% medical fluorescein in saline was applied to each patient’s nasal cavity; droplets were visualized on a white sheet covering the patient and a white apron worn by the health care worker. The patients’ masks were kept below their noses but were covering their mouths.

“During the placement and removal of the catheter, the health care worker was always standing sideways or even behind the patient, and they always stood higher relative to the patient to ensure that when there was aerosol or droplet spread, it was not in their direction,” Dr. Verbeure said during his virtual presentation.

During placement for HRM and removal for MII-pH, aerosol particles (excluding those that were 0.3 mcm), decreased significantly. Otherwise, particle counts remained stable. “This shows that these investigations do not generate additional aerosol [particles], which is good news,” Dr. Verbeure said.

When the air purifier was present, placement and examination for HRM were associated with significant reductions in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm), whereas removal caused a slight uptick in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm) that did not decline after 5 minutes. “This was actually a surprise to us,” Dr. Verbeure said. “Because we now had an air purifier present, and we expected an even lower number of particles.”

He suggested that the purifier may have been reducing particle counts during HRM examination, thereby lowering baseline values before removal, making small changes more noticeable; or the purifier may have been causing turbulence that spread particles during removal. Whether either of these hypotheses is true, Dr. Verbeure noted that particle counts were never higher than at the start of the examination. Fluorescein visualization showed “surprisingly little droplet spread,” Dr. Verbeure said, apart from some contamination around the patient’s neck.

“Esophageal investigations do not seem to generate additional [aerosol] particles,” Dr. Verbeure concluded. “So wearing the recommended protective gear and also considering the right positioning of the health care worker relative to the patient is important to keep performing this daily clinical routine.” To avoid droplet spread, health care workers should “be aware of the [patient’s] neck region and the direction of the catheter,” Dr. Verbeure added.
 

SORTing the results

According to Mahdi Najafi, MD, associate professor in the department of anesthesiology at Tehran University of Medical Sciences, Iran, and adjunct professor at Schulich School of Medicine & Dentistry, Western University, London, Ontario, the findings offer valuable insights. “[This study] is very important for at least two reasons: The extent of using this procedure in patient care, especially in the critical care setting, and the paucity of information for COVID-19 transmission and route of transmission as well,” Dr. Najafi said in an interview.

Yet he cautioned against generalizing the results. “We cannot extend the results to all nasogastric tube intubations,” Dr. Najafi said. “There are reasons for that. The tube for manometry is delicate and flexible, while the nasogastric tube used for drainage and GI pressure release – which is used commonly in intensive care and the operating room – is larger and rather rigid. Moreover, the patient is awake and conscious for manometry while the other procedures are done in sedated or unconscious patients.”

He noted that nasogastric intubation is more challenging in unconscious patients, and often requires a laryngoscope and/or Magill forceps. “The result [of using these instruments] is coughing, which is undoubtedly the most important cause of aerosol generation,” Dr. Najafi said. “It can be regarded as a drawback to this study as well. The authors would be better to report the number and/or severity of the airway reactions during the procedures, which are the main source of droplets and aerosols.”

To reduce risk of coronavirus transmission during nasogastric intubation of unconscious patients, Dr. Najafi recommended the SORT (Sniffing position, nasogastric tube Orientation, contralateral Rotation, and Twisting movement) maneuver, which he introduced in 2016 for use in critical care and operating room settings.

“The employment of anatomical approach and avoiding equipment for intubation were devised to increase the level of safety and decrease hazards and adverse effects,” Dr. Najafi said of the SORT maneuver. “The procedure needs to be done step-by-step and as smooth as possible.”

In a recent study, the SORT maneuver was compared with nasogastric intubation using neck flexion lateral pressure in critically ill patients. The investigators concluded that the SORT maneuver is “a promising method” notable for its simple technique, and suggested that more trials are needed.

The investigators and Dr. Najafi reported no conflicts of interest.

Gastrointestinal symptoms and chronic fatigue may persist months after the COVID-19 virus infection resolves, results of a recent cohort-controlled study suggest.

About 5 months after SARS-CoV-2 infection, relative risks of loose stools, somatization, and chronic fatigue were increased by approximately two- to three fold, compared to individuals who had not been infected, according to study results presented at the annual Digestive Disease Week® (DDW).

These longer-term consequences of SARS-CoV-2 appeared to be more severe in patients who had experienced diarrhea during the acute infection, according to investigator Daniele Noviello, MD, a second-year resident in gastroenterology and hepatology at the University of Milan.

This is the first cohort-controlled study that specifically investigates gastrointestinal symptoms and somatoform disorders, Dr. Noviello said in a virtual presentation of the results.

“Based on our data, chronic fatigue, gastrointestinal, and somatoform symptoms may have a common postinfectious origin, and they should be investigated in the follow-up of SARS-CoV-2 patients,” he said.
 

Links between SARS-CoV-2 and gastrointestinal symptoms

Gastrointestinal symptoms are known to be relatively common during acute infection. According to Dr. Noviello, the most frequent gastrointestinal symptom associated with SARS-CoV-2 is diarrhea, occurring in 4% to nearly 40% of patients in case series to date.

However, data on the longer-term gastrointestinal impacts of SARS-CoV-2 remain scarce.

In one noncontrolled cohort study in China, loss of appetite, nausea, acid reflux, and diarrhea were seen in 15%-24% of patients 3 months after the infection, Dr. Noviello said. In another cohort study in China, diarrhea and vomiting were reported in 5% of patients 6 months after infection.

In any case, it is known that viral, bacterial, and protozoal infections of the gastrointestinal tract are a risk factor for development of functional disorders including irritable bowel syndrome (IBS), functional dyspepsia, and chronic fatigue, according to Dr. Noviello.

Accordingly, the results of the present study suggest that SARS-CoV-2 also “may affect the brain-gut axis in the long term,” Dr. Noviello and coauthors wrote in an abstract of the study.

It is plausible that SARS-CoV-2 infection could be a trigger for longer-term gastrointestinal symptoms, especially given the previous evidence linking infections and IBS symptoms, or postinfectious IBS, said Juan Pablo Stefanolo, MD, a physician with the neurogastroenterology and motility section, Hospital de Clínicas José de San Martín, Buenos Aires University.

“If it is demonstrated [that SARS-CoV-2 infection is a trigger], the microbiota-gut-brain axis concept in IBS pathophysiology is reinforced,” Dr. Stefanolo said in an interview.

In the meantime, practitioners may want to take into account COVID-19 infection history in the evaluation of a patient with IBS-like symptoms and, in case of a known positive COVID-19 result in an IBS patient, be aware of the possibility of symptom exacerbation, Dr. Stefanolo said.
 

Pandemic in Italy: Unique study opportunity

The severe outbreak in the Milan region early in the COVID-19 pandemic provided a “unique opportunity” to assess the long-term impact of infection on gastrointestinal and extraintestinal somatoform symptoms, said Dr. Noviello.

The investigators sent an online questionnaire to patients who had a molecular diagnosis of SARS-CoV-2 infection by nasal swab between February and April of 2020. To form a control group, they also sent questionnaires to hospital employees and health care providers who had tested negative over that same time period.

In all, 378 questionnaires were completed by 177 SARS-CoV-2–positive individuals and 201 controls. The SARS-CoV-2–positive patients were somewhat older (about 44 years vs. 40 years for controls), were less often female (40% vs. 61%), had a lower education level, and smoked less than did controls, according to the investigators.

A mean of 4.8 months had elapsed between the time of SARS-CoV-2 infection and when the questionnaires were compiled, said Dr. Noviello.

In the acute phase, diarrhea was the most common gastrointestinal symptom among virus-positive individuals, occurring in about 50% compared to 20% of controls (P < .001), data show. Other symptoms reported by 40% of SARS-CoV-2–infected individuals included fever, dyspnea, loss of smell or taste, weight loss, myalgia, arthralgia, and asthenia in the acute phase controls in the acute phase, Dr. Noviello said.
 

Persistent gastrointestinal symptoms after SARS-CoV-2

Persistent symptoms included loose stools, as measured by the Bristol Stool scale, occurring in 17.8% of SARS-CoV-2–positive individuals, but only 9.3% of the SARS-CoV-2–negative controls, according to Dr. Noviello, with an adjusted risk ratio of 1.88 (95% confidence interval, 0.99-3.54).

Chronic fatigue symptoms, as measured by the Structured Assessment of Gastrointestinal Symptoms questionnaire, were reported by about 30% of SARS-CoV-2–positive patients and about 15% of controls, for an adjusted risk ratio of 2.24 (95% CI, 1.48-3.37), according to Dr. Noviello’s presentation.

The mean t-score on the Symptom Checklist–12 for somatoform disorders was higher for the virus-positive patients compared to controls, according to Dr. Noviello. The scores were 54.6 and 50.5, respectively, with an adjusted score difference of 3.6 (95% CI, 1.0-6.2).

The longer-term sequelae of SARS-CoV-2 infection might be more severe in individuals who experienced diarrhea during acute infection, according to Dr. Noviello. In a post hoc analysis, reports of irritable bowel syndrome and loose stools were significantly higher in SARS-CoV-2–infected individuals who had diarrhea in the acute phase compared to those who did not experience diarrhea, he said.

Somatoform disorder scores were significantly higher, and reports of headache, back pain, and chronic fatigue were significantly more common, in individuals who had diarrhea at the time of SARS-CoV-2 infection, he added.

Dr. Noviello and coauthors reported no competing interests related to the study. Dr. Stefanolo had no disclosures to report.
 

Gastrointestinal symptoms and chronic fatigue may persist months after the COVID-19 virus infection resolves, results of a recent cohort-controlled study suggest.

About 5 months after SARS-CoV-2 infection, relative risks of loose stools, somatization, and chronic fatigue were increased by approximately two- to three fold, compared to individuals who had not been infected, according to study results presented at the annual Digestive Disease Week® (DDW).

These longer-term consequences of SARS-CoV-2 appeared to be more severe in patients who had experienced diarrhea during the acute infection, according to investigator Daniele Noviello, MD, a second-year resident in gastroenterology and hepatology at the University of Milan.

This is the first cohort-controlled study that specifically investigates gastrointestinal symptoms and somatoform disorders, Dr. Noviello said in a virtual presentation of the results.

“Based on our data, chronic fatigue, gastrointestinal, and somatoform symptoms may have a common postinfectious origin, and they should be investigated in the follow-up of SARS-CoV-2 patients,” he said.
 

Links between SARS-CoV-2 and gastrointestinal symptoms

Gastrointestinal symptoms are known to be relatively common during acute infection. According to Dr. Noviello, the most frequent gastrointestinal symptom associated with SARS-CoV-2 is diarrhea, occurring in 4% to nearly 40% of patients in case series to date.

However, data on the longer-term gastrointestinal impacts of SARS-CoV-2 remain scarce.

In one noncontrolled cohort study in China, loss of appetite, nausea, acid reflux, and diarrhea were seen in 15%-24% of patients 3 months after the infection, Dr. Noviello said. In another cohort study in China, diarrhea and vomiting were reported in 5% of patients 6 months after infection.

In any case, it is known that viral, bacterial, and protozoal infections of the gastrointestinal tract are a risk factor for development of functional disorders including irritable bowel syndrome (IBS), functional dyspepsia, and chronic fatigue, according to Dr. Noviello.

Accordingly, the results of the present study suggest that SARS-CoV-2 also “may affect the brain-gut axis in the long term,” Dr. Noviello and coauthors wrote in an abstract of the study.

It is plausible that SARS-CoV-2 infection could be a trigger for longer-term gastrointestinal symptoms, especially given the previous evidence linking infections and IBS symptoms, or postinfectious IBS, said Juan Pablo Stefanolo, MD, a physician with the neurogastroenterology and motility section, Hospital de Clínicas José de San Martín, Buenos Aires University.

“If it is demonstrated [that SARS-CoV-2 infection is a trigger], the microbiota-gut-brain axis concept in IBS pathophysiology is reinforced,” Dr. Stefanolo said in an interview.

In the meantime, practitioners may want to take into account COVID-19 infection history in the evaluation of a patient with IBS-like symptoms and, in case of a known positive COVID-19 result in an IBS patient, be aware of the possibility of symptom exacerbation, Dr. Stefanolo said.
 

Pandemic in Italy: Unique study opportunity

The severe outbreak in the Milan region early in the COVID-19 pandemic provided a “unique opportunity” to assess the long-term impact of infection on gastrointestinal and extraintestinal somatoform symptoms, said Dr. Noviello.

The investigators sent an online questionnaire to patients who had a molecular diagnosis of SARS-CoV-2 infection by nasal swab between February and April of 2020. To form a control group, they also sent questionnaires to hospital employees and health care providers who had tested negative over that same time period.

In all, 378 questionnaires were completed by 177 SARS-CoV-2–positive individuals and 201 controls. The SARS-CoV-2–positive patients were somewhat older (about 44 years vs. 40 years for controls), were less often female (40% vs. 61%), had a lower education level, and smoked less than did controls, according to the investigators.

A mean of 4.8 months had elapsed between the time of SARS-CoV-2 infection and when the questionnaires were compiled, said Dr. Noviello.

In the acute phase, diarrhea was the most common gastrointestinal symptom among virus-positive individuals, occurring in about 50% compared to 20% of controls (P < .001), data show. Other symptoms reported by 40% of SARS-CoV-2–infected individuals included fever, dyspnea, loss of smell or taste, weight loss, myalgia, arthralgia, and asthenia in the acute phase controls in the acute phase, Dr. Noviello said.
 

Persistent gastrointestinal symptoms after SARS-CoV-2

Persistent symptoms included loose stools, as measured by the Bristol Stool scale, occurring in 17.8% of SARS-CoV-2–positive individuals, but only 9.3% of the SARS-CoV-2–negative controls, according to Dr. Noviello, with an adjusted risk ratio of 1.88 (95% confidence interval, 0.99-3.54).

Chronic fatigue symptoms, as measured by the Structured Assessment of Gastrointestinal Symptoms questionnaire, were reported by about 30% of SARS-CoV-2–positive patients and about 15% of controls, for an adjusted risk ratio of 2.24 (95% CI, 1.48-3.37), according to Dr. Noviello’s presentation.

The mean t-score on the Symptom Checklist–12 for somatoform disorders was higher for the virus-positive patients compared to controls, according to Dr. Noviello. The scores were 54.6 and 50.5, respectively, with an adjusted score difference of 3.6 (95% CI, 1.0-6.2).

The longer-term sequelae of SARS-CoV-2 infection might be more severe in individuals who experienced diarrhea during acute infection, according to Dr. Noviello. In a post hoc analysis, reports of irritable bowel syndrome and loose stools were significantly higher in SARS-CoV-2–infected individuals who had diarrhea in the acute phase compared to those who did not experience diarrhea, he said.

Somatoform disorder scores were significantly higher, and reports of headache, back pain, and chronic fatigue were significantly more common, in individuals who had diarrhea at the time of SARS-CoV-2 infection, he added.

Dr. Noviello and coauthors reported no competing interests related to the study. Dr. Stefanolo had no disclosures to report.
 

Gastrointestinal symptoms and chronic fatigue may persist months after the COVID-19 virus infection resolves, results of a recent cohort-controlled study suggest.

About 5 months after SARS-CoV-2 infection, relative risks of loose stools, somatization, and chronic fatigue were increased by approximately two- to three fold, compared to individuals who had not been infected, according to study results presented at the annual Digestive Disease Week® (DDW).

These longer-term consequences of SARS-CoV-2 appeared to be more severe in patients who had experienced diarrhea during the acute infection, according to investigator Daniele Noviello, MD, a second-year resident in gastroenterology and hepatology at the University of Milan.

This is the first cohort-controlled study that specifically investigates gastrointestinal symptoms and somatoform disorders, Dr. Noviello said in a virtual presentation of the results.

“Based on our data, chronic fatigue, gastrointestinal, and somatoform symptoms may have a common postinfectious origin, and they should be investigated in the follow-up of SARS-CoV-2 patients,” he said.
 

Links between SARS-CoV-2 and gastrointestinal symptoms

Gastrointestinal symptoms are known to be relatively common during acute infection. According to Dr. Noviello, the most frequent gastrointestinal symptom associated with SARS-CoV-2 is diarrhea, occurring in 4% to nearly 40% of patients in case series to date.

However, data on the longer-term gastrointestinal impacts of SARS-CoV-2 remain scarce.

In one noncontrolled cohort study in China, loss of appetite, nausea, acid reflux, and diarrhea were seen in 15%-24% of patients 3 months after the infection, Dr. Noviello said. In another cohort study in China, diarrhea and vomiting were reported in 5% of patients 6 months after infection.

In any case, it is known that viral, bacterial, and protozoal infections of the gastrointestinal tract are a risk factor for development of functional disorders including irritable bowel syndrome (IBS), functional dyspepsia, and chronic fatigue, according to Dr. Noviello.

Accordingly, the results of the present study suggest that SARS-CoV-2 also “may affect the brain-gut axis in the long term,” Dr. Noviello and coauthors wrote in an abstract of the study.

It is plausible that SARS-CoV-2 infection could be a trigger for longer-term gastrointestinal symptoms, especially given the previous evidence linking infections and IBS symptoms, or postinfectious IBS, said Juan Pablo Stefanolo, MD, a physician with the neurogastroenterology and motility section, Hospital de Clínicas José de San Martín, Buenos Aires University.

“If it is demonstrated [that SARS-CoV-2 infection is a trigger], the microbiota-gut-brain axis concept in IBS pathophysiology is reinforced,” Dr. Stefanolo said in an interview.

In the meantime, practitioners may want to take into account COVID-19 infection history in the evaluation of a patient with IBS-like symptoms and, in case of a known positive COVID-19 result in an IBS patient, be aware of the possibility of symptom exacerbation, Dr. Stefanolo said.
 

Pandemic in Italy: Unique study opportunity

The severe outbreak in the Milan region early in the COVID-19 pandemic provided a “unique opportunity” to assess the long-term impact of infection on gastrointestinal and extraintestinal somatoform symptoms, said Dr. Noviello.

The investigators sent an online questionnaire to patients who had a molecular diagnosis of SARS-CoV-2 infection by nasal swab between February and April of 2020. To form a control group, they also sent questionnaires to hospital employees and health care providers who had tested negative over that same time period.

In all, 378 questionnaires were completed by 177 SARS-CoV-2–positive individuals and 201 controls. The SARS-CoV-2–positive patients were somewhat older (about 44 years vs. 40 years for controls), were less often female (40% vs. 61%), had a lower education level, and smoked less than did controls, according to the investigators.

A mean of 4.8 months had elapsed between the time of SARS-CoV-2 infection and when the questionnaires were compiled, said Dr. Noviello.

In the acute phase, diarrhea was the most common gastrointestinal symptom among virus-positive individuals, occurring in about 50% compared to 20% of controls (P < .001), data show. Other symptoms reported by 40% of SARS-CoV-2–infected individuals included fever, dyspnea, loss of smell or taste, weight loss, myalgia, arthralgia, and asthenia in the acute phase controls in the acute phase, Dr. Noviello said.
 

Persistent gastrointestinal symptoms after SARS-CoV-2

Persistent symptoms included loose stools, as measured by the Bristol Stool scale, occurring in 17.8% of SARS-CoV-2–positive individuals, but only 9.3% of the SARS-CoV-2–negative controls, according to Dr. Noviello, with an adjusted risk ratio of 1.88 (95% confidence interval, 0.99-3.54).

Chronic fatigue symptoms, as measured by the Structured Assessment of Gastrointestinal Symptoms questionnaire, were reported by about 30% of SARS-CoV-2–positive patients and about 15% of controls, for an adjusted risk ratio of 2.24 (95% CI, 1.48-3.37), according to Dr. Noviello’s presentation.

The mean t-score on the Symptom Checklist–12 for somatoform disorders was higher for the virus-positive patients compared to controls, according to Dr. Noviello. The scores were 54.6 and 50.5, respectively, with an adjusted score difference of 3.6 (95% CI, 1.0-6.2).

The longer-term sequelae of SARS-CoV-2 infection might be more severe in individuals who experienced diarrhea during acute infection, according to Dr. Noviello. In a post hoc analysis, reports of irritable bowel syndrome and loose stools were significantly higher in SARS-CoV-2–infected individuals who had diarrhea in the acute phase compared to those who did not experience diarrhea, he said.

Somatoform disorder scores were significantly higher, and reports of headache, back pain, and chronic fatigue were significantly more common, in individuals who had diarrhea at the time of SARS-CoV-2 infection, he added.

Dr. Noviello and coauthors reported no competing interests related to the study. Dr. Stefanolo had no disclosures to report.